Organ Sys Path 1 & 2: Lymphohematopoietic

Lymphadenomegaly

Enlarged node

Lymphadenitis

Inflamed node

Lymphadenopathy

Diseased node

1. Usually big

   1. Hyperplasia

      1. Sinus histiocytosis (macrophage hyperplasia)

      2. Follicular hyperplasia (B-lymphocytes)

      3. Paracortical hyperplasia (T-lymphocytes)

   2. Inflammation

      1. Acute or chronic lymphadenitis

   3. Neoplasia

      1. Primary (lymphoma)

      2. Metastatic

2. Small

   1. Atrophy

      1. Lymphoid atrophy

Responses to injury of lymph nodes

Sinus histiocytosis

Macrophage hyperplasia

Follicular hyperplasia

1. (B-lymphocytes)

2. Most common type of hyperplasia seen

3. Plasma cell makes antibodies (vaccination!)

Paracortical hyperplasia

1. (T-lymphocytes)

2. Lymphocytes regulate inflammation

Acute lymphadenitis

1. Gross

   1. Red and edematous

   2. Enlarged

   3. Soft

   4. Taunt capsule

   5. Bulge on cut surface

   6. Necrotic/suppurative areas

      1. Suppurative bacteria

   7. +/- hemorrhage

Streptococcus equi ssp. equi (Strangles)

1. Inhaled or ingested → attach to tonsils → enter lymphatics

   1. Drain to regional lymph node → large abscesses

2. Guttural pouch empyema

3. Compression of the pharynx → Respiratory stridor

4. Dysphagia

5. Abscess may rupture through skin

Bastard strangles

Metastatic abscess formation in other organs

Purpura hemorrhagica

1. Type III hypersensitivity reaction necrotizing vasculitis

2. From repeated natural exposure or vaccination in horses that have had strangles

Jowl abscesses

1. Acute lymphadenitis in pigs

   1. Streptococcus porcinus

1. Chronic suppurative inflammation (abscess)

2. Granulomatous inflammation

Inflammatory types of chronic lymphadenitis

Corynebacterium pseudotuberculosis

1. Chronic suppurative inflammation (abscess)

   1. ___

      1. Ruminants: caseous lymphadenitis

      2. Horses: pigeon fever

Rhodococcus equi

Chronic suppurative inflammation (abscess)

1. Pyogranulomatous enterotyphlocolitis and lymphadenitis

2. Large abdominal abscesses of mesenteric lymph nodes

Johne’s disease

1. Chronic lymphadenitis

   1. Granulomatous inflammation

      1. ___

         1. Mycobacterium avium spp. paratuberculosis (MAP)

         2. Granulomatous enteritis and lymphadenitis of mesenteric LNs

Tuberculosis

1. Chronic lymphadenitis

   1. Granulomatous inflammation

      1. Mycobacterium ___ complex

Tuberculosis

What disease should we think about when seeing mineralized lymph nodes in a cow?

Fungal infections

1. Chronic lymphadenitis

   1. Granulomatous inflammation

      1. ___

         1. Cryptococcosis (dogs)

         2. Histoplasmosis

         3. Blastomycosis

Porcine circovirus 2 (PCV2)

1. Postweaning multisystemic wasting syndrome (PMWS)

   1. Poor body condition

   2. Interstitial pneumonia

   3. Enlarged lymph nodes

      1. Lymphoid depletion/necrosis

      2. Granulomatous lymphadenitis

   4. Porcine dermatitis and nephropathy syndrome (PDNS)

      1. Necrotizing vasculitis

      2. Kidney and skin affected

      3. Similar LN changes

Primary lymph node neoplasia (lymphoma)

1. Always malignant

2. Arises from lymphoid tissue outside of bone marrow

   1. Leukemia phase

B cell lymphoma

Which type of lymphoma?:

CD79a, Pax5, CD20 immunomarkers

T cell lymphoma

Which type of lymphoma?:

CD3 immunomarkers

Multicentric

Multiple lymph nodes involved; other visceral organs may be involved

Alimentary

Involves GI tract and regional lymph nodes

Mediastinal

Mediastinum or thymus are involved; young animals, T cell origin

Cutaneous

Skin and draining lymph nodes involved

Miscellaneous

Lymphomas of kidney, brain, eye, etc.

Multicentric

1. Lymphoma in dogs

   1. ___ is the most common form

      1. Can see hypercalcemia of malignancy due to PTHrP secretion

Alimentary, IBD, T cell, B cell

1. Lymphoma in cats

   1. ___ lymphoma is most common

      1. ___ → lymphoma

      2. Usually ___

         1. EATL type 1

         2. EATL type 2: most common

      3. Some ___

         1. Stomach

         2. Ileocecocolic junction

Bovine leukosis virus (BLV)

1. Lymphoma in cattle

   1. Associated with ___

      1. 70% → no clinical signs, carriers

      2. 30% → leukocytosis

      3. 1-2% → lymphoma

Heart, uterus, lymph nodes, abomasum (HULA)

Common sites of cattle lymphoma

Viral infections, distemper

1. Atrophy

   1. ___ → EHV-1, CSF, BVD, ___, parvovirus

   2. Malnutrition and cachexia

   3. Glucocorticoids

   4. Aging

   5. Radiation

2. Congenital

   1. SCID

   2. Congenital hereditary lymphedema

3. Lack of antigenic stimulation

   1. SPF animals

Mucosa-associated lymphoid tissue (MALT)

1. Anatomic location

   1. Bronchus-associated (BALT)

   2. Tonsils (pigs– CSF)

   3. Nasal-, larynx-, and auditory tube-associated (NALT, LALT, ATALT)

   4. Gut-associated (GALT)-- Peyer’s patches

      1. Depleted in BVDV, CDV

   5. Conjunctiva-associated (CALT)

2. Main points

   1. Act like little lymph nodes

   2. Portal of entry for many diseases

   3. Atrophy with viral lymphoid depletion

D

What is the most common type of lymphoma in a dog?

A) GI

B) Splenic

C) Hepatic

D) Multicentric

B

What type of thymic neoplasia is most common in goats?

A) Mesenchymal

B) Epithelial

C) Round cell

D) Neuroendocrine

A

What tissue response is more common in chronic splenitis?

A) Macrophage hyperplasia

B) Neutrophilic inflammation

C) Fibrin and necrosis

D) Abscess formation

B

What disease is acutely fatal in bovine targeting endothelial cells and causing acute diffuse splenomegaly?

A) Mycobacteriosis

B) Anthrax

C) Amyloidosis

D) Truperella endocarditis

C

Which of the following is a primary location for hemangiosarcoma?

A) Aorta

B) Brain

C) Liver

D) Lymph node

1. Lymphoid atrophy

   1. Inadequate supply from bone marrow

   2. Lymphocytolysis

2. Inflammation

   1. Rare

3. Hemorrhage/hematoma

4. Neoplasia

Thymus responses to injury

1. Environmental toxins

   1. Halogenated aromatic hydrocarbons

   2. Heavy metals

   3. Mycotoxins

2. Chemotherapeutic drugs

3. Malnutrition and cachexia

4. Infectious agents

   1. Canine distemper virus

Causes of thymic atrophy

Thymitis

1. Uncommon

2. Viral infections more commonly cause thymic atrophy

3. Bacteremia

4. Epizootic bovine abortion (Pajaroellobacter abortibovis)

5. Neorickettsia helminthoeca (salmon poisoning disease) in dogs

Hematoma (thymic hemorrhage)

1. Young dogs

   1. Anticoagulants

   2. Dissecting aortic aneurysms

   3. Trauma

   4. Idiopathic/spontaneous

      1. At time of neuter

Thymic lymphoma (lymphoid), thymoma (epithelial)

Types of thymic neoplasia

Thymic lymphoma (lymphoid)

1. T cells

2. Young cats and cattle

Thymoma (epithelial)

1. Older goats and dogs (and rabbits!)

2. Associated with

   1. Myasthenia gravis

      1. Autoantibodies toward acetylcholine receptors → megaesophagus → aspiration pneumonia

   2. Immune-mediated polymyositis

Myasthenia gravis, megaesophagus

What condition is thymoma associated with, and what does this condition cause?

1. Red pulp

   1. Blood

   2. Macrophages

   3. Antigen-presenting cells

2. White pulp

   1. Lymphocytes (B cells)

   2. Antigen-presenting cells

Components of spleen

Lymphocytes (B cells)

Main component of white pulp of spleen

Macrophages

Main component of red pulp of spleen

Hematogenous

Portal of entry/pathway of spread of thymus

Hematogenous spread

Direct penetration (uncommon; thick capsule)

Portals of entry/pathways of spread of spleen

1. Lymphoid hyperplasia (PALS, follicles)

   1. Diffuse

   2. Nodular

2. Atrophy

Response to injury of white pulp of spleen

Splenitis

1. Red pulp

   1. Inflammation: ___

      1. Acute

         1. Neutrophils

         2. Fibrin and necrosis

         3. Abscesses

      2. Chronic

         1. Macrophage hyperplasia

            1. Fungal/protozoal agents

            2. Intracellular bacteria

Macrophage hyperplasia

1. Red pulp

   1. ___

      1. Chronic hemolytic disease

         1. Immune-mediated hemolytic anemia (IMHA)

         2. Chronic splenic congestion

Erythrophagocytosis

Phagocytosis of RBCs

Congestion

1. Diffuse acute splenomegaly

   1. ___

      1. Barbiturates

      2. Splenic torsion

         1. Most common in dogs and pigs

         2. Gastric dilation and volvulus (GDV) in deep-chested dog

Hyperemia

Diffuse acute splenomegaly

1. ___

   1. Septicemia

      1. Bacillus anthracis

         1. Ruminants

         2. Gram-positive bacillus

         3. Ingested → LN → Septicemia

         4. Exotoxins → degrade endothelial cells → massive hemorrhage

         5. Salmonellosis

Hyperemia

More blood than normal going to the body’s tissues or organs

Septicemia

Bacteria from one part of the body entering the bloodstream

Acute hemolytic anemia

Diffuse acute splenomegaly

1. Dilation of red pulp vascular spaces with erythrocytes and erythrophagocytes

2. IMHA

3. Isoimmune hemolytic anemia

   1. Horses and pigs

4. Hemotropic parasites

   1. Ruminants: babesiosis, Anaplasma marginale

   2. Swine: Mycoplasma haemosuis

   3. Cats: Mycoplasma haemofelis, Cytauxzoon felis

5. Equine infectious anemia

Macrophage hyperplasia, phagocytosis

Acute bloody spleen becomes a chronic meaty spleen over time due to ___ and ___ of cells, debris, or foreign agents/material plus/minus cellular infiltrates

Congestion, acute hyperemia, acute hemolytic anemia

Three causes of acute diffuse splenomegaly

Phagocytosis of cells, debris, or foreign agents/material; proliferation or infiltration of cells; storage diseases

Three causes of chronic diffuse splenomegaly

Antigenic stimulation

Diffuse chronic splenomegaly

1. ___

   1. Proliferation or infiltration of cells

   2. Diffuse lymphoid hyperplasia

      1. Same as for lymph nodes

      2. Nonspecific

      3. Chronic ___

         1. Bacterial endocarditis

         2. Pyometra

         3. Pleuritis

         4. Heartworm disease

         5. UTI

         6. Severe periodontitis

Infectious disease

Diffuse chronic splenomegaly

1. ___

   1. Diffuse granulomatous inflammation

      1. Intracellular organisms that infect macrophages

         1. Bacteria

            1. Mycobacteriosis

            2. Salmonella

            3. Tularemia

         2. Protozoa

            1. Leishmaniasis

            2. Toxoplasmosis

         3. Systemic mycosis

            1. Histoplasmosis

            2. Coccidiomycosis

            3. Blastomycosis

Extramedullary hematopoiesis (EMH)

Diffuse chronic splenomegaly

1. ___

   1. Bone marrow failure

   2. Increased demand (anemia)

   3. Abnormal cell signaling

Neoplasia

Diffuse chronic splenomegaly

1. ___

   1. Can be diffuse or nodular

   2. Histiocytic sarcoma

   3. Mast cell tumor

      1. More common in cats

   4. Lymphoma

Storage disease

Diffuse chronic splenomegaly

1. ___

   1. Storage of material

   2. Lysosomal storage disease

   3. Amyloid

      1. Many different types

         1. Most common

            1. Serum amyloid A (SAA)

            2. Chronic inflammation

      2. Positive with Congo-red stain

Hematoma, acute infarction, neoplasia, incomplete splenic contraction

Four causes of acute nodular splenomegaly

Hematoma

Spleen bloody nodules

1. ___

   1. Bulging, dark red, solitary mass

   2. Can resolve or rupture

      1. Rupture leads to hemoperitoneum, hypovolemic shock, and death

   3. Can form from trauma or other nodules like nodular hyperplasia

Acute infarction

Spleen bloody nodules

1. ___

   1. Hypercoagulable states

   2. Neoplasia

   3. Cardiovascular disease

   4. Infectious etiologies

      1. Classical swine fever– pigs

      2. Septicemia

Hemangiosarcoma

Spleen bloody nodules

1. ___

   1. Tumor of blood vessels

   2. Most common primary sites

      1. Spleen

      2. Liver

      3. Right auricle

      4. Retroperitoneal space

   3. Frequent metastasis

      1. Lungs

      2. Primary tumor sites

      3. Brain

      4. Muscle (less often)

Spleen, liver, right auricle, retroperitoneal space

Most common primary sites of hemangiosarcoma

Lungs, primary tumor sites, brain

Where does hemangiosarcoma frequently metastasize?

Nodular hyperplasia, neoplasia, granuloma, abscess

Four causes of chronic nodular splenomegaly

Hemorrhage

A meaty nodule can become a bloody nodule due to ___.

Neoplasia

Spleen meaty nodules

1. ___

   1. Primary

      1. Lymphoma

      2. Histiocytic sarcoma

      3. Hemangiosarcoma

      4. Stromal tumor

   2. Metastatic

Granulomas

Spleen meaty nodules

1. ___

   1. Organisms that cause diffuse granulomatous splenitis can also cause nodular infections

      1. Intracellular bacteria

      2. Protozoa

      3. Fungus

Abscess

Spleen meaty nodules

1. ___

   1. Not very common

   2. Streptococcus equi

      1. Bastard strangles

   3. Rhodococcus equi

   4. Fusobacterium necrophorum

Aging changes, wasting/cachectic diseases, splenic contraction

Three causes of splenic atrophy

Massive hemorrhage, fight or flight response

Two causes of splenic contraction

Siderotic plaques

1. Areas of historical hemorrhage?

2. Common in aged dogs

3. Incidental

4. Don’t remove the spleen if you see this during a surgery!

Rupture

1. Trauma

   1. HBC, KBH (kicked by horse), SOBP (stepped on by person)

2. Splenomegaly can predispose

3. Leads to hemoabdomen

Splenosis

Spleen tissue breaks off main organ and implants at another site in the body

Splenules

1. Accessory spleens on serosal surfaces

2. Can be secondary to splenic rupture

3. Rarely, they can be sites for neoplasia formation