Lymphoid Tissue Pathology

What are primary lymphoid organs/tissues where B lymphocytes develop/mature?

- Bone marrow and cloacal bursa

What animals are susceptible to infectious bursal disease (IBD)? What does this virus do?

- Young chickens and turkeys are very susceptible

- Virus destroyed B cells in secondary lymphoid tissues (e.g., GALT, MALT, BALT, tonsils) and mature cells in primary lymphoid tissues (e.g., cloacal bursa)

What is the mortality of Infectious Bursal Disease?

- ~20%; Survivors are often immunocompromised

What are primary lymphoid organs where T lymphocytes develop/mature?

- Thymus

In primary lymphoid organs, precursor T cells are "screened" to ensure that they can do what two things?

1) Can recognize "self" MHC molecules (and therefore antigen presentation)

2) Do NOT recognize self antigens as foreign (otherwise autoimmune disease may result)

What percentage of pre-T cells "graduate" the thymus to live in secondary immune organs/tissues

- <5%

What cells are critical to "teaching" new T cells in the thymus?

- Thymic epithelial cells are antigen presenting cells

Describe the general anatomy of the thymus. Describe its color.

- Paired cervical lobes (left and right), an intermediate lobe at the thoracic inlet, and a thoracic lobe, which may be bilobed.

- Pale colored tissue compared to the heart/lung adjacent

Is age-appropriate involution of the thymus considered a lesion?

- No

Thymic hypoplasia/aplasia occurs with what disease processes?

- Equine SCID

- Canine SCID

What breed is equine SCID common in? What is its inheritance?

- Arabian; Arabian cross breeds

- Autosomal recessive disorder

What does equine SCID result in?

- Severe lymphopenia; recurrent infections lead to death

- Thymus is small/undetectable due to marked lymphoid hypoplasia

- Spleen/lymph nodes are small

Describe the prognosis of equine SCID.

- Affected foals rarely live beyond 5 months of age

- Heterozygous carriers live longer; have greater risk of developing sarcoids

In what breeds is canine SCID common? What is its inheritance?

- X-linked SCID in Basset Hounds and Cardigan Welch Corgis

- Autosomal recessive SCID in Jack Russel Terriers

Describe the clinical picture of canine SCID.

- Similar to equine SCID with similar abnormalities in lymphoid tissues

Viral diseases commonly cause what in lymphoid tissues?

- Viral diseases commonly cause lymphoid tissue destruction

What does Porcine Circovirus 2 cause?

- Inflammation and cell death in lymphoid tissues including thymus

- Post-weaning multi-systemic wasting syndrome (PMWS)

What does Beak and Feather Disease cause?

- Causes lymphoid necrosis in psittacines (mostly parrots)

- Bone marrow, bursa, and thymus atrophy

- Severe anemia and leukopenia

How does Beak and Feather Disease Virus enter the body/spread systemically?

- Virus enters via GI tract (GALT, bursa) then spreads to the liver, thymus, epidermis, etc.

What are some viruses which cause thymic atrophy?

- CDV

- BVDV

- EHV-1

- Swine fever virus

- Canine and feline Parvovirus

- FIV

What are thymomas? Are they typically benign or malignant?

- Thymic epithelial tumors that usually contain many lymphocytes

- Usually benign but can compress adjacent structures

Thymomas are common in which species?

- Goats

Dogs (and rarely cats) with thymoma are at high risk for what?

- Immune mediated disease (e.g. myasthenia gravis, immune-mediated polymyositis, and subsequently megaesophagus and aspiration pneumonia can occur)

What two neoplasias can cause thymic enlargement?

- Thymoma

- Lymphoma (neoplasia of thymic lymphocytes)

What is the function of lymph nodes?

- Filtration of blood and lymph to identify non self-antigens and generate immune response

- APCs present antigens to T cells

What are the APCs?

- B cells

- Macrophages

- Dendritic cells

What types of antigens are easy/difficult for the immune system to identify?

- Non-self antigens (viral, bacterial, fungal, etc.) are easy for the immune system to identify

- Tumor cell antigens are difficult because they are essentially mutated "self" so T cells with high affinity receptors for these cells are deleted to promote self-tolerance instead of maturing into cytotoxic cells that can kill the cancer

What are the components of a lymph node?

- Stroma: Capsule/trabeculae/reticulum

- Cortex (Outer cortex: Lymphoid follicules, B lymphocytes)

- Paracortex (Inner cortex: T lymphocytes)

- Medulla (sinuses and medullary cords)

- Blood vessels

- Lymphatic vessels and sinuses

- Sinus histiocytes

What is a lymphocenter?

- Node or group of nodes consistently in same place, always drains same "lymphosome" (region of tissue which drains into a certain group of nodes)

What are broad categories of causes for enlargement of a lymph node?

- Hyperplasia (reactive increase in cell numbers)

- Inflammation (acute or chronic lymphadenitis)

- Neoplasia (primary lymphoma/histiocytic sarcoma; metastatic)

What are broad categories of causes for small lymph nodes?

- Atrophy (viruses)

What are the two patterns of lymph node enlargement? What form of spread are they each associated with and what are causes of each?

- Generalized = Hemic spread (systemic infection/inflammation; hemic neoplasia like lymphoma or leukemia)

- Single or regional = Lymphatic spread (Disease in region drained by those nodes)

What are causes of reactive hyperplasia and histiocytosis in a lymph node?

- Chronic antigenic stimulation (allergic/inflammatory disease like dental/skin disease or IBD; acute or chronic infection like demodicosis)

What lymph nodes are expected to be enlarged in each of the following scenarios?

A. Dental disease

B. Inflammatory bowel disease

C. Blood-borne infections

A. Reactive hyperplasia of mandibular nodes

B. Reactive hyperplasia of mesenteric nodes

C. Generalized hyperplasia of lymph nodes

Inflammation of a lymph node is known as _______________.

- Lymphadenitis

What are causes of lymphadenitis?

- Drainage of an inflammed/infected lesions

- Inflammation/infection within the node itself (FIP, Juvenile cellulitis/Puppy strangles, equine strangles, Mycobacterium/fungal infection, Salmon poisoning)

Describe the etiology and type of inflammation seen in the lymph node in each of the following disease processes:

A. FIP

B. Juvenile cellulitis ("Puppy strangles")

C. Equine strangles

D. Mycobacterium/fungal infection

A. Viral -> Pyogranulomatous inflammation

B. Sterile/immune-mediated -> Suppurative or pyogranulomatous inflammation

C. Bacterial -> Suppurative inflammation or abscesses

D. Bacterial/fungal -> Granulomatous inflammation

In a lymph node responding to infection, you will often see a mixture of ______________ and ______________ within the node.

- Inflammation

- Reactive hyperplasia

What is caseous lymphadenitis? What is it caused by?

- Infectious, contagious disease of small ruminants

- Cornybacterium pseudotuberculosis

What structures are affected by caseous lymphadenitis in goats and sheep?

- Peripheral lymph nodes affected (more common in goats)

- Internal lymph nodes and organs affected (more common in sheep)

Describe the appearance of lymph nodes affected by caseous lymphadenitis grossly and histologically?

- Gross: Lymph nodes contain thick purulent material that forms "onion skin" layers over time

- Histology: Lymphadenitis with abscesses, gram-positive coccobacilli

What other species can be affected by caseous lymphadenitis?

- Horses (pigeon fever -> Abscesses in the pectoral region)

- Cattle

- Pigs

- Camelids

- Birds

- People (zoonotic risk)

How does caseous lymphadenitis persist in a herd?

- Via chronically infected animals

- In environment

What are differentials for hemic neoplasia originating within a node? What about hemic neoplasia spreading to a node?

- Originating within node: Lymphoma; histiocytic sarcoma

- Spreading to node: Lymphoma; histiocytic sarcoma; mast cell neoplasia; plasma cell neoplasia; leukemia

Carcinomas usually spread via the ________________.

- Lymphatics

How can secondary lymphoid tissues serve as entry points for infection?

- Bacteria can enter M cells over Peyer's patches and set up a chronic infection after being phagocytosed by macrophages (i.e. Paratuberculosis; aka Johne's disease)

The spleen is an example of a __________ lymphoid organ where immune responses happen.

- Secondary

What are functions of the spleen?

- Filtration of blood to remove infections, abnormal/aging cells

- Storage of blood for release in "emergencies"

- Extramedullary hematopoiesis

What does splenectomy impair?

- Impairs ability to remove bacterial and protozoal infections (and impairs immune responses to viruses)

What does it mean to say dogs have a true "sinusoidal" spleen?

- They're best at "pitting" RBCs (removing abnormalities such as Heinz bodies) and at phagocytosing abnormal/infected RBCs

Which species have spleens which can store "lots" of RBCs (i.e. have storage spleens)? What triggers contraction of the spleen?

- Horses, dogs, and cats

- Autonomic nervous system can trigger contraction via smooth muscle in capsule, trabeculae

Which species carries out a lot of extramedullary hematopoiesis?

- Rodents

Describe the white pulp and red pulp of the spleen.

- White pulp: Lymphocyte and histiocyte rich tissue where immune responses happen

- Red pulp: Vascular portion of the spleen where blood filtration and storage occur

What structures make up the white pulp of the spleen?

- Lymphoid follicles

- PALS (lymphoid sheath around vessels)

- PAMS (macrophage sheath around vessels)

Describe the structure of the spleen.

- Dense, organized, and encapsulated (Thick, fibrous capsule) organ

What are the two types of splenomegaly?

- Uniform (diffuse)

- Nodular

What are differential diagnoses for diffuse, "bloody" splenomegaly?

- Reduced vascular flow into and out of the spleen (splenic torsion)

- Intravenous barbiturates

- Acute hyperemia due to septicemia (Anthrax, salmonellosis)

- Acute hemolysis (Babesiosis, EIA, acute IMHA)

What are differential diagnoses for diffuse, "firm" splenomegaly?

- Increase in cells (Infiltrative neoplasia, EMH, chronic hemolysis/IMHA, granulomatous inflammation)

- Increase in non-cellular material: Amyloidosis and storage disorders

What are differential diagnoses for nodular, "bloody" splenomegaly?

- Acute infarcts

- Hematomas (trauma)

- Hemangiosarcoma

What are the benefits and risks of aspirating a splenic mass prior to surgery?

- Benefits: Low yield; ~5% of splenic HSA are diagnosed with cytology

- Risks: Aspiration of the cavitated or cystic spleen can cause rupture

What are causes of acute splenic infarcts in dogs?

- Hypercoagulable stress

- Valvular endocarditis may cause multi-organ infarcts, including spleen

What are causes of acute splenic infarcts in cattle?

- Traumatic reticulitis

- Splenic abscesses

- Portal vein thrombosis

- Arterial thrombosis

- Valvular endocarditis may cause multi-organ infarcts, including spleen

What are differential diagnoses for nodular, "firm" splenomegaly?

- Lymphoid nodular hyerplasia

- Primary neoplasia

- Metastatic neoplasia

- Granulomas and abscesses (i.e. migrating FB in cattle from reticulum)

What are causes of primary nodular neoplasia in the spleen?

- Round cell: Lymphoma, mast cell, histiocytic sarcoma (these can also be diffuse)

- HSA

What are causes of metastatic nodular neoplasia in the spleen?

- Sarcoma

- Round cell neoplasia

- Rarely carcinoma (likes to metastasize through the lymphatics which the spleen doesn't have)

What are causes of bacterial abscesses in the spleen?

- Streptococcus spp.

- Rhodococcus equi

- Cornybacterium psuedotuberculosis

What are viral causes of granulomas/abscesses in the spleen?

- FIP in cats (pyogranulomas)

What are causes of splenic rupture?

- Trauma (HBC or high rise)

What are causes of accessory spleens?

- Congenital (choristoma)

- Acquired (from trauma)

What are siderofibrotic plaques (iron scars) in the spleen?

- "Iron scars" located on the capsule, usually at the edge of the spleen which are benign and common in older dogs

_____________ can be used to phenotype lymphocytes and other WBCs. How does this work?

- Antibodies

- They bind to specific surface receptors specific to a WBC type

What antibodies are used to phenotype B cells and T cells?

- B cells: CD79a or CD20

- T cells: CD3 (subtypes are CD4 (Th) and CD8 (Tc)

Antibodies can be used to phenotype/"label" lymphocytes and other WBCs in which forms?

Can label cells/tissues sections on slides:

- ICC on unstained smears (cytology/aspirate)

- IHC on sections (histopathology/biopsy)

Can label cells in suspension:

- Flow cytometry

What types of WBCs can antibody phenotyping be used on?

- Normal and neoplastic cells in any tissue

What does PARR stand for? What is its purpose?

- PCR for Antigen Receptor Rearrangement

- Tests to see if a lymphocyte population is clonal (monoclonal; all cells have identical surface receptors) or polyclonal (cells all have different surface receptors)

On PARR, if a population is clonal, what does this indicate? What about if it is polyclonal?

- Clonal: Lymphoid neoplasia (lymphoma or lymphoid leukemia)

- Polyclonal: Reactive population

PARR is currently available for which species?

- Dogs and cats

What samples can be used for PARR?

- Can be run on stained dried cytology slides, biopsy tissues (fresh or in formalin/paraffin), liquid samples (blood/fluids)

If a PARR is diagnostic for neoplasia, does it provide any further information?

- Usually provides an accurate phenotype (B vs. T) as well