Hemolymphatic Dz (Bone Marrow, Thymus, Spleen, LN)

Define hematopoiesis

Bone marrow production of cells (myeloid and lymphoid) that is based on peripheral need

Young animal bone marrow characteristics

More active red tissue, less fat

Adult animal bone marrow characteristics

More inactive fatty tissue but there are still sites for hematopoiesis. Extra-medullary hematopoiesis occurs in the spleen

Regenerative anemia clincal/pathological findings

Icterus, splenomegaly, hemorrhage

Regenerative anemia bone marrow findings

Erythroid hyperplasia

Non-Regenerative anemia clincal/pathological findings

Myelofibrosis/bone marrow disease, pallor

Non-Regenerative anemia bone marrow findings

Absence of erythroid precursors/cytosis of other lineages

Causes of non-regenerative anemia

-infectious

-toxins

-medications, estrogens

-CKD

-iron deficiency

-neoplasia

What is aplastic anemia?

Decrease in red and white blood cells leading to pallor, thrombocytopenia, neutropenia, and petechiae/echymoses

Infectious causes of aplastic anemia

-Ehrlichia (dogs and cats)

-Parvovirus (dogs and cats)

-FeLV/FIV (cats)

-EIA (horses)

What is a therapeutic cause of aplastic anemia in dogs?

Estrogen administration

Main lesion of myelofibrosis

Bone marrow fibrosis with macrophages with iron pigment

What are the 3 mechanisms for myelofibrosis development?

1. Scar formation after necrosis

2. High concentration of growth factors with bone marrow injury or activation

3. Idiopathic

What are 3 causes of bone marrow necrosis leading to myelofibrosis?

1. Neoplasia (leukemia/metastatic)

2. Infectious (FeLV/sepsis)

3. Toxins

What are the toxins leading to necrosis and myelofibrosis?

-carprofen

-chemo

-estrogen

-metronidazole

-mitotane

-phenobarbital

-heavy metals

-irradiation

Serous atrophy of fat lesion and main cause

Lesion = gelatinous transformation of bone marrow

Cause = starvation/emaciation

Causes of non-neoplastic lymphocytosis in dogs and cats

o Age/antigenic stimulation in cats

o Epinephrine in cats

o Chronic infection

o Ehrlichia canis

o Addison's disease

o Hyperthyroidism in cats

o Paraneoplastic lymphocytosis

o Cattle = Bovine Leukosis Virus (BLV)

Acute leukemia

-Poorly differentiated

-CD34 expression

-Very poor prognosis (9-56 days)

->20% blast cells in marrow or blood

-Pancytopenia (anemia, neutropenia, thrombocytopenia)

-Median age 7-8 years but wide range in dogs

-Necropsy = pale mucous membranes, bone marrow highly cellular but pancytopenia, splenomegaly, lymph node involvement

Chronic leukemia

-CD8 expression (T cell)

-CD21 expression (B cell)

-Often has incidental lymphocytosis

-Necropsy = splenomegaly, anemia, lymphadenopathy, highly cellular bone marrow

Negative prognostic factors in B cell CLL

-Boxers have shorter survival time

-High lymphocyte count >60,000 = shorter survival

-Higher Ki-67 = shorter survival

Explain the benefits of using flow cytometry in cases of lymphocytosis in dogs and cats

o Distinguishes homogenous from heterogenous expansions

o Identifies aberrant antigen expression

o Provides prognostic information

List three clinical abnormalities that can be seen with multiple myeloma

o Hyperglobulinemia (overproduction by neoplastic plasma cells)

o Hypercalcemia (bone osteolysis)

o Pancytopenia (neoplastic plasma cells replace the normal cells)

What abnormality would you except in the bone marrow in a dog with MM?

Markedly increased plasma cells in the bone marrow (>20-30%)

Identify which cell is infected in equine infectious anemia

Macrophages

How does thrombocytopenia and anemia develop in EIA?

Immune mediated hemolysis/destruction of platelets

THYMUS SECTION

List 3 viral diseases in dogs or cats that can affect the thymus

o Parvovirus (causes injury AND necrosis)

o Distemper virus

o FIV

List 3 viral disease in other species that can affect the thymus

-EHV-1

-BVDV

-PCV-2

What is the cause of Post-weaning multi-systemic wasting syndrome?

Porcine Circovirus-2

What inflammation is present with PCV-2?

Granulomatous inflammation with multinucleated cells with cytoplasmic viral inclusions

What pathology is seen with PCV-2?

• Thymic enlargement

• Lymph node enlargement

• Interstitial pneumonia

• Poor body condition

Define the neoplastic cell of a thymoma

Neoplastic epithelial cells

3 paraneoplastic syndromes with a thymoma & pathophysiology

Myasthenia gravis and megaesophagus — defective antigen presentation leading to auto-antibodies against AchRs, neuromuscular dysfunction in esophagus

Thymoma associated lymphocytosis — expansion of non-neoplastic T lymphocytes in response to the tumor. Note that this is different from lymphoma because lymphoma is neoplastic lymphocyte proliferations.

Exfoliative dermatitis — immune mediated attack on epidermal cells

What types of cells can you see in an aspirate of a thymoma?

Double positive T cells (heterogenous population on flow cytometry)

Differentials for a cranial mediastinal mass

o Lymphoma

o Thymoma

o Hemangiosarcoma

o Neuroendocrine tumor

Cattle thymic lymphoma

-less than 2 years old

-NOT associated with BLV

Cats thymic lymphoma

-typically 1-3 years old

-CAN be associated with FeLV/FIV

Dogs thymic lymphoma

-mean age 8 years

-hypercalcemia common

Goats thymic lymphoma

-3 years of age

-mediastinal involvement frequent

Pigs thymic lymphoma

-less then 2 years old

-spontaneous

Thymoma vs. Thymic Lymphoma

SPLEEN SECTION

Recognize gross photos of diffuse enlargement and nodular enlargement of the spleen

List non-neoplastic causes of diffuse soft enlargement of the spleen

Splenic entrapment/volvulus/torsion

Barbiturate euthanasia/anesthesia/sedation

Acute hyperemia/septicemia (anthrax, salmonella, erysipelothrix)

Acute hemolytic anemia (babesiosis, hemolytic crises in EIA, IMHA)

Why does acute hyperemia/septicemia cause splenomegaly?

this occurs because the number of pathogenic bacteria in circulation exceeds capacity of the splenic macrophages

What is a typical component of soft expansions of the spleen?

Blood

What species are primarily affected by anthrax?

Ruminants (peracute hemorrhage and death)

What is the pathogenesis of anthrax?

1. Ingestion, inhalation, or wound

2. Endospores germinate in macrophages for 1-14 days

3. Spread to lymph nodes and systemic circulation

4. Toxins lead to decreased phagocytosis, increased capillary permeability (edema), and delayed clotting

What can be seen on impression smears of the spleen in anthrax?

Large gram + rods

What should be done to manage an outbreak of anthrax?

-Carcasses, bedding, feces, etc must be cremated or deep burial

-Vaccinate exposed animals to contain and prevent disease

List three differentials for nodular, soft, enlargement of the spleen

1. Hematomas

2. Hemorrhagic infarcts (classical swine fever)

3. Neoplasia (hemangiosarcoma)

Important note about classical swine fever and african swine fever

African swine fever cause diffuse soft splenomegaly but often the lesions are indistinguishable from classical swine fever

Tumor cell type hemangiosarcoma

Endothelial cells

3 breeds commonly affected with hemangiosarcoma

-Golden retrievers

-German shepherds

-Portuguese water dogs

What are the two primary sites of hemangiosarcoma?

1. Spleen

2. Right auricle of heart

Hemangiosarcoma gross changes

single or multifocal to coalescing dark red-purple masses which are variably bloody/cavitated to solidly cellular on cut section

Hematomas gross changes

red to dark red, soft, bulging, usually solitary mass of varying size

Hemorrhagic infarcts gross changes

wedge shaped hemorrhagic lesions (chronic = pale)

List three causes of diffuse firm enlargement of the spleen

1. Diffuse granulomatous disease (histoplasmosis)

2. Neoplasms (round cell tumors)

3. Storage disease/amyloidosis

Important note about lymphoma

Can be diffuse firm OR nodular firm

Important note about storage disease/amyloidosis

RARE AF

List differentials for firm nodules in the spleen

-Lymphoid and complex nodular hyperplasia

-Primary OR metastatic neoplasia

-Granulomas/abscesses

-Extramedullary hematopoiesis

2 bacteria that cause splenic abscesses

1. Rhodococcus equi

2. Trueperella pyogenes

2 bacteria that cause splenic granulomas

1. Tularemia

2. Mycobacteria

Nodular firm neoplasia

Primary = lymphoma, histiocytic sarcoma, splenic stromal sarcomas, solid hemangiosarcomas, myelolipomas

Metastatic = sarcomas, carcinomas, malignant round cell tumors

Cell of origin histiocytic sarcoma

Monocytic/histiocytic origin (dendritic cells and macrophages)

Important note about histiocytic sarcoma pattern

Can be diffuse firm and nodular firm

What are common tissues affected by histiocytic sarcoma?

Spleen, lung, liver, skin, articular surface of joints, bone marrow

What are common breeds affected by histiocytic sarcoma?

-Bernese mountain dogs

-Flat-coated retrievers

-Golden retrievers

LN/LYMPHATICS SECTION

Recognize normal architecture and pattern of LNs

Where do T cells live in the LN?

Paracortex

Where do histiocytes and macrophages live in the LN?

Medulla

Where do B cells live in the LN?

Cortex

Enteric lymphangiectasia/itis in the dog gross findings

Will see the lymphatics and pinpoint dots inside of the mucosa

Enteric lymphangiectasia/itis in the dog clinical findings

chronic diarrhea, wasting, hypoproteinemia, lymphopenia, hypocalcemia, hypocholesterolemia

Enteric lymphangiectasia/itis in the dog histo

Dilated lymphatics

What is the cause/pathogenesis of serosal lesions?

Intestinal lipogranulomatous lymphangitis = accumulations of granulomatous inflammation forming white masses

Enteric lymphangiectasia VS intestinal lipogranulomatous lymphangitis

4 causes of chylothorax

o Idiopathic

o Trauma

o CHF

o Chest tumors

Clin path finding of chylothorax

lymphopenia due to loss of lymphocytes in fluid

Causes of lymph node atrophy

-Primary immunodeficiency disease

-Lack of antigenic stimulation

-Viral infections

-Cachexia & malnutrition

-Aging

-Radiation

Viruses that can injure lymphoid tissue

-Parvovirus

-FIV

-BVDV

-Distemper

-Ehrlichia

Name common species to be affected by Yersinia pestis

Squirrels, prairie dogs, rabbits, wood rats

How is plague spread?

Bite by infected flea or consumption of infected animal

Gross findings of plague in cats

Fever, loss of appetite, lethargy, enlarged LNs

Name three other bacterial causes of lymphadenitis/adenomegaly

-Mycobacterium avium ssp paratuberculosis

-Rhodococcus equi

-Streptococcus equi ssp equi

Name a fungal cause of lymphadenitis/adenomegaly

Histoplasmosis

Name two causes of bacterial lymphadenitis in horses

-Streptococcus equi ssp equi (Strangles)

-Rhodococcus equi

Streptococcus equi ssp equi

-Term for systemic spread = bastard strangles

-Purpura hemorrhagica (type III) from repeated exposure

Rhodococcus equi

-Foals up to 6 months old causing bronchopneuonia

-50% develop progranulomatous ulcerative enterotyphlocolitis of Peyer's patches

-Pyogranulomatous inflammation with phagocytized bacteria

3 bacterial causes of bacterial lymphadenitis in cattle or sheep

1. Johne's Disease

2. Bovine Tuberculosis

3. Caseous Lymphadenitis

Johne's disease cause

mycobacterium avium paratuberculosis

Johne's disease gross findings

Enteritis and granulomatous lymphadenitis

Johne's disease stain

Acid fast within macrophages

Bovine tuberculosis cause

Mycobacterium bovis

Bovine tuberculosis gross findings

Necrotic and suppurative/abscessed lymph nodes

Bovine tuberculosis human infection

Raw milk

Caseous lymphadenitis cause

gram + intracellular bacterium corynebacterium pseudotuberculosis

Caseous lymphadenitis transmission

enters through skin wounds —> drain to regional LN —> disseminate in lymph and blood