SYS Path 1

hemolymphatics,

What is included in myeloid tissue

bone marrow, any circulating cells derived there

RBC, neutrophils, eosinophils, basophils, etc

What is included in lymphoid tissue

Lymph nodes, spleen, thymus, circulating lymphocytes, bursa of Fabricius

What are primary lymphoid organs

bone marrow, thymus

where lymph is born

What are secondary lymphoid organs

lymph nodes, tonsils, spleen, MALT

Three main places where hematopoiesis occurs

1. Yolk sac: embryo → shifts to liver and spleen in fetus

2. Liver and spleen: fetus → shifts to bone marrow prior to birth

• When mature: is location of extramedullary hematopoiesis

3. Bone marrow: young → all marrow spaces

• When mature: marrow spaces of the axial bones, proximal humerus and femur

3 main patterns to consider in gross pathology of bone marrow

Colour → yellow (fat), red (hematopoietic tissue), white (fibrosis, necoris)

Location → epiphyseal, metaphyseal, diaphyseal, endosteal

Distribution → diffuse/general, focal, multifocal

Reasons for diffuse and generalized decreased/empty/replaced hematopoietic bone marrow

Myelofibrosis

Nutritional deficiencies

Infectious agents → viral, protazoal, fungi

Destruction → radiation, chemotherapy, drugs, estrogen, immune mediated

Reasons for focal and multifocal decreased/empty/replaced hematopoietic bone marrow

Multiple myeloma

Non-myeloid/lyphoid neoplasia

Metastatic neoplasia

Reasons for diffuse extra hematopoietic bone marrow

Age (physiological, NOT pathological in young)

Hyperplasia (longstanding increased demand)

Myeloid/lymphoid leukemia

Myelodysplastic syndrome

Patchy and multifocal reasons for extra hematopoeitic bone marrow

Leukemia, lymphoma

Endosteal reasons for extra hematopoeitic bone marrow

Hyperplasia (>3 weeks of increased demand)

Reasons for hemorrhagic bone marrow

Trauma

Bone cyst

Infarction

Necrosis

Reasons for inflamed bone marrow

Myelitis

Infectious agents

What are 4 main reasons that bone marrow is decreased, empty, or replaced

1. Increased destruction → immune mediated, toxic, infectious, radiation

2. Reduced production or function → hereditary, nutritional deficiencies

3. Demand exceeds production capacity → overwhelming bacterial infection

4. Replacment (myelophthisis) → myelofibrosis, diffuse neoplasia

What is this, and what causes it

Hyperplasia of bone marrow

Loss of red blood cells/ platelets due to hemorrhage, hemolytic anemia, etc

Inflammatory stimulus from liver abscess, pneumonia, etc.

What is this, and what causes it

Serous atrophy of fat (gelatinous transformation of fat)

From cachexia or starvation → the fat is metabolized, bone marrow reticular cells produce mucoid substance to replace

What is this, and what causes it

Neoplasia

Myeloid/lymphoma (leukemia, lymphoma, multiple myeloma)

Non-myeloid/lymphoid (hemangiosarcoma, metastatic neoplasia)

What is this, and what causes it

Infection → osteomyelitis, myelitis

What are the 3 main functions of the thymus

Differentiation, selection, and maturation of T cells

• T cell receptor rearrangement

• Positive selection (MHC binding)

• Negative selection (self-reactive)

only 2% of T cells exit the thymus

3 zones of the thymus

1. Subcapsular: T-cells from the bone marrow enter the thymus

2. Cortex: positive/negative selection, and TCR rearrangement

3. Medulla: negative selection

2 main types of cell in the thymus

1. Lymphocytes

2. Epithelial cells (hassall’s corpuscles)

What does a normal thymus look like on gross pathology

Located intrathoracic mediastinum cranial to the heart and ventralto trachea, in ruminants sometimes cervical

Is pink and lobulated in a young animal, involutes as the animal ages (shrinks) when sexual maturity approaches

When would you suspect a lesion in the thymic resion

Masses in the region, diffuse expansion of the thymus

How will a thymic lesion be detected in small animals?

Respiratory symptoms, look at thoracic radiographs

• Intrathoracic mediastinal masses/cysts, or hemorrhage

Detection of paraneoplastic syndromes

How will thymic lesions be detected in large animals

Cervical swelling (masses, cysts)

What are some reasons for absent or small thymus

Involution (PHYSIOLOGICAL)

Inadequate nutrition

Stress (increased glucocorticoids)

Infectious agents (virus)

Intoxicants (leads, mercury)

Medical treatment (radiation, chemotherapy)

Aplasia

What are some reasons for diffuse enlargement of thymus

Variation (physiological!)

Hyperplasia (repeated immunization)

Neoplasia (lymphoma)

What are some reasons for focal and localized enlarged thymus

Custs (persist during involution, or acquired)

Neoplasia (thymoma)

What are some reasons for an inflamed thymus

Thymitis (uncommon)

What are some reasons for hemorrhagic thymus

Etiologic vs. idiopathic

What is this

involuted thymus (should be tightly packed)

What is this

panleukopenia thymus

No obvious cortical/medullary distinction

What are 3 important features of signalment/history for thymic hemorrhage

age

access to rodenticide

trauma

What are 3 common differential diagnoses for thymic hemorrhage

1. idiopathic hemorrhage

2. anticoagulant toxicity (rodenticide)

3. traumatic hemorrhage

What are some antimortem diagnostic tests for thymic hemorrhage

cbc

clotthing time

What is a proposed pathogenesis to spontaneous idiopathic thymic hemorrhage

Thymic involution (this MUST be occuring) → thin walled vessels, no longer with structural support from adjacent parenchyma → slight trauma or sudden increase in BP → hemorrhage

This is a diagnosis of exclusion, must first rule out toxicitiy and trauma

What are the main histologic findings here

Absence of any evidence of thymic involution

extensive hemorrhage

Distinct cortical medullary distinction

Pathogenesis of rodenticide toxicity

Ingestion of anticoagulant rodenticide → Vit K deficiency → clotting factors consumed without replacement → hemorrhagge

What is this

thymoma

What is this

lymphoma

What are the two types of thymic neoplasia

Thymoma, thymic carcinoma

Lymphoma

(generally uncommon)

How to differentiate thymoma and lymphoma

Thymoma → focal, localized, with epithelial or lymphoid tissue

Lymphoma → diffuse

Paraneoplastic syndromes of dogs and cats

Dogs = myasthenia gravis

Cats = exfoliative dermatitis

What is the pathogenesis of thymoma to secondary myasthenia gravis in dogs

Thymoma → autoantibodies develop against thymic myoid cells, which have Ach receptors → antibodies in systemic circulation → binds to AchRs on postsynaptic membrane at the neuromuscular junction → prevents Ach from binding → prevents muscle contraction → muscle weakness

3 min causes of thymitis (rare)

1. Porcine circovirus type 2 in pigs

2. Epizootic bovine abortion": foothill abortion in cattle

3. Salmon poisoning disease in dogs (neorickettsia helminthoeca)

Cell types in the stroma of spleen

1. endothelium

2. smooth muscle cells

3. fibroblasts

cell types of red pulp in spleen

1. erythrocytes

2. histiocytes (macrophages)

The function of red pulp in the spleen

1. Innate immune function

2. Storage

3. extra medullary hematopoiesis

Cell types in the white pulp of the spleen

lymphocytes

histiocytes (dendritic cells)

What is the function of the white pulp in spleen

Adaptive immmune function

When would you suspect a splenic lesion

Patient with hemoabdomen

Abdominal imaging shows splenic mass, or splenomegaly

What are some reasons for bloody nodules in the spleen

Neoplasia

Hematoma

Acute infarct

What are some reasons for enlarged nodule in the spleen

Neoplasia

Abscess/granuloma

Nodular hyperplasia

Non-acute infarct

Siderotic plaques

What are some reasons for extra, or multiple spleens

Ectopic

Fracture

Splenosis

What are some reasons for diffuse bloody spleen

Acute septicemia/infection

Barbituates

Volvulus/torsion

Acute IMHA

What are some reasons for diffuse enlargement of the spleen

Neoplasia

Extramedullary hematopoiesis

Phagocytosis

Storage material

Chronic IMHA

Subacute/chronic infection

What is this

splenic venous infarct, acute

What is this

splenic infarct, chronic and fibrosing

What is this

Siderotic plaques

BENIGN common splenic lesion in dogs

What type of histiocytic sarcoma is this (+ ddx)

Macrophagic histiocytic sarcoma → is diffusely meaty, in red pulp

lymphoma and amyloidosis are ddx when examining grossly

What type of histiocytic sarcoma is this (+ ddx)

Dendritic cell → in follicles, and nodular

Metastatic neoplasia and abscesses are ddx when examining grossly

2 main reasons for bloody splenic nodules

Hematoma (can occur secondary to other lesions)

Hemangiosarcoma

4 main reasons for meaty splenic nodules

1. Primary neoplasia → benign (myelolipoma, follicular lymphoma), malignant (splenic sarcoma, lymphoma, histiocytic sarcoma)

2. Metastatic neoplasia

3. Nodular hyperplasia

4. Granuloma/abscess

What is a reason for a raised lesion (but not nodules)

Acute infarct (bloody)

Non-acute infarct (meaty)

Siderotic plaques (meaty)

What is this, and what are some differential diagnoses

barbituates

volvulus

acute septicemia (extra blood incoming)

What is this, and what causes it

Amyloidosis of spleen

From buildup of amyloids in extracellular space

Bloody, diffuse reasons for splenomegaly

Acute septicemia/infection

Barbituates

Volvulus/torsion

Acute IMHA

Acute infectious disease

Meaty, diffuse reasons for splenomegaly

Neoplasia (histiocytic sarcoma macrophage, lymphoma)

Phagocytosis

Chronic IMHA

Amyloidosis

Chronic infectious disease

Extramedullary hematopoiesis

What is splenosis

Acquired, autoimplantation of splenic tissue into other places

can be from trauma, with seeding of splenic tissue

What are 3 functions of lymph nodes

1. lymph filtering

2. Surveillance and processing incoming antigens

3. B-lymphocyte maturation, plasma cell development

What are the main regions of the lymph node

Cortex → lymphoid follicles

Paracortex → diffuse lymphoid tissue

Medulla → cords of lymphocytes/plasma cells and macrophages

Sinuses → lymph (subcapsular, paratrabecular, medullary)

What are some ways an animal with lymph node lesions will present

Multiple enlarged peripheral lymph nodes → painful or painless

Single enlarged peripheral lymph node → painful, painless

Multiple, or single enlarged internal lymph nodes, identified with medical imaging

Some reasons for small lymph nodes

Immunodeficiency

Cachexia/malnutrition

Aging

Viral infection → other than RETROVIRUSES

Radiation

What are some reasons for multifocal/focal enlarged lymph nodes

Metastatic neoplasia

Follicular hyperplasia

Aute/chronic lymphadenitis

Granulomatous

Caseous

Abscessation

What are some reasons for diffuse enlargement of lymph nodes

Viral infection of RETROVIRUS only

Primary neoplasia

Diffuse hyperplasia

Acute/chronic lymphadenitis

Sinus histiocytosis

Reasons for lymphadenomegaly OR lymphadenopathy in whole body vs. focal

systemic infection/inflammation/neoplastic process vs. localized infection/inflammation/neoplastic process

What is this, and what are some reasons for it

Sinus histiocytosis/macrophage hyperplasia

Due to response to draining antigens

Draining from catchment area

What is lymphadenitis

Non reactive hyperplasia of lymph node: inflammation has taken over

Acute and subactue lymphadenitis leads to chronic

How does strangles affect the lymph nodes

Streptococcus equi subsp. equi

Affects mandibular and retropharyngeal lymph nodes

When it spreads to abdominal lymph nodes → called bastartd strangles

• Lymphadenitis from peripheral lymph nodes leads to liquefactive necrosis, which drains to abdomen/lungs, etc

What is this and its pathogenesis

Caseous Lymphadentitis

skin wound (shearing in sheep) → Corynebacterium pseudotuberculosis penetrates skin → drains to regional lymph node → systemic circulation → localizes to internal lymmph nodes, lungs, spleen

What is this

granulomatous lymphadenitis

What are some causes of granulomatous lymphadenitis (infectious)

Corynebacterium pseudotuberculosis in sheep/goats

Rhodococcus equi in horses

PCV-2 in pigs

Mycobacterium bovis/avium complex in cattle

Mycobacterium paratuberculosis (Johne’s disease) in cattle

Fungal infection of various species → aspergillosis, histoplasmosis, blastomycosis, cryptococcosis

Feline infectious peritonitis in cats

2 neoplasias of the lymph node

1. Lymphoma → neoplastic lymphocytes forming solid tumors, secondary leukemia

2. Leukemia → neoplastic lymphocytes in bone marrow and blood, secondary formation of solid tumors

What is this

canine or feline lymphoma

LN is bulging and there is no cortical/medullary distinction

What are the features of sporadic bovine lymphoma

Not bovine leukemia virus

Multicentric → calves <6 months, in LN, organs, bone marrow

Thymic → 6-24 months, massive thymic enlargement

Cutaneous → 6-24 months, multifocal skin tumors

What are the features of enzootic bovine leukemia

From bovine leukemia virus

Multicentric: 4-8 years

• widely distributedin LNs

• In uterus, abomasum, myocardium

• Lymhpoid tissue behind eyes, and in CNS

3 types of equine lymphoma

1. alimentary/internal → GI and regional LN, liver, spleen, peritoneum

2. Multicentric → peripheral LN, abdominal LN, mediastinal mass

3. Cutaneous

What is this

equine lymphoma

What is the normal function and characteristics of lymphatics

Transporting lymph

Grossly, not typically visible

Histologically, endothelial lined vessels, which are difficult to differentiate from veins

4 main types of lymphatic lesions

1. Lymphedema: accumulation of fluid in tissue secondary to blockage/damage (obstruction not common, arteriovenous shunt)

2. Lymphangitis: infection/inflammation of lymph vessels (usually occurs with lymphadenitis, secondary lesion)

3. Lymphangiectasia: abnormally dilated lymph vessels (developmental)

• Acquired → obstruction, but usually idiopathic

• Protein losing enteropathy clinically, with dilated lacteals

4. Lymphangiosarcoma: neoplasia of the lymphatics

What is this

Lymphangitis, Johne’s Disease

What is this

Lymphangiectasia

Lacteals in the middle of villi are very extended, not allowing absorption of proteins (PLE)

What is the function of MALT

Acts as sentinels, protecting mucosal barriers

B-cell development in Peyer’s patches (ruminants) and bursa of fabricius (birds)

What is this

Peyer’s patches in ruminant

continuous strip of lymphoid tissue in goat intestine

What causes atrophy of MALT

viral infection, malnutrition/cachexia, aging, chemo, radiation

What causes hyperplasia of MALT

antigenic stimulation