Pathology of haematopoietic system 1

What tissues does the haematopoietic system involve? List some examples

Myeloid tissue —> bone marrow, blood cells, mononuclear phagocyte system

Lymphoid tissue —> lymph nodes, spleen, thymus, accessory lymphoid tissue

Define anaemia

• Is a reduction in the number of erythrocytes and/or the haemoglobin concentration.

• It is a clinical sign and not a disease

• Caused by abnormally high RBC loss/destruction or decreased RBC formation.

What are the features of infectious anaemia?

• Predominantly induce extravascular haemolysis —> hyperbilirubinaemia, jaundice, anaemia and splenomegaly

• Lesions may be subtle or profound with gross finding depending on severity

List some examples of infectious anaemia

• Equine infectious anaemia

• Anaplasmosis

• Haemotropic mycoplasma

• Babesiosis

• Trypanosomiasis

• Theileriosis

Describe the pathogenesis of EIA (equine infectious anaemia aka swamp fever)

• Infects cells of the monocyte-macrophage system, incl. megakaryocytes

• Premature removal of platelets and erythrocytes coated in immune complexes

What is the name of the virus causing EIA? How is it transmitted?

• Equine infectious anaemia virus (lentivirus)

• Transmitted by flies, contaminated needles (mechanical not biological)

Describe the gross findings expected with EIA

• Petechial haemorrhages esp. in kidney

• Oedema of abdominal wall and suspensory ligaments

• Enlarged liver and spleen

• Red bone marrow (increased haematopoietic cells replacing fat)

Describe the histological findings expected with EIA

Increased cellularity of Bone marrow without increase in megakaryocytes

Describe the pathogenesis of anaplasmosis

• Obligate intracellular bacterial infection of erythrocytes

• Transmitted by ixodid ticks (biologically) and blood sucking flies, needles etc. (mechanically)

What is represented by the pale circular cells vs the purple dots?

Pale circular cells = RBCs

Purple dots = anaplasma bacterial cells

What are the aetiological agents cause anaplasmosis?

• A. marginale

• A. centrale (cattle)

• A. ovis (sheep & goats)

How does anaplasmosis present grossly?

Pallor and jaundice, no pathognomic lesions

How does anaplasmosis present histologically?

What aetiological agents cause haemotropic mycoplasma?

• M.haemofelis (cats),

• M. haemocanis (spleenectomised/immunosuppressed dogs),

• M. wenyonii (cattle)

Describe the pathogenesis of babesiosis

• Apicomplexan protozoan, infects and replicates in erythrocytes -> lysis of RBCs

• Transmitted by ticks, wide range of mammals

How does babesiosis present histologically?

See 2/4 pear-shaped merozoites(piroplasm) on blood smear

What aetiological agents cause babesiosis?

Cattle: Babesia bovis> B. bigemina in disease severity

How does babesiosis present grossly?

Congestion of gray matter in CNS

Recall the function, structure and circulation of lymph nodes

Function:

• Filtration of lymph

• Immune response

Structure:

• Outer cortex -> follicles (mostly B cells)

• Inner cortex -> paracortex (mostly T cells)

• Medulla -> mostly B cells and macrophages

What is lymphadenopathy?

• Enlargement of lymph node(s) of unknown cause

• Can be localised or generalised

What can be the causes of enlarged lymph nodes?

• Lymphadenitis

• Lymphoid hyperplasia

• Hyperplasia of the monocyte/macrophage system

• Primary neoplasia e.g. lymphoma

• Secondary Neoplasia

What can be the causes of small lymph nodes?

• Lymphoid atrophy

• Lymph node degeneration/necrosis

• Lymph node hypoplasia

What is lymphadentitis?

An inflammatory response to an infectious agent within the node (as opposed to reactive hyperplasia which is an antigen driven immunologic response)

What is the difference between acute lymphadenitis and chronic lymphadenitis?

How does chronic suppurative lymphadenitis present grossly?

• Swollen/enlarged lymph node with pus filled centre = lymph node abscess

• Can fistulate to the skin surface

• Response to pyogenic bacteria

How does chronic suppurative lymphadenitis present histologically?

• Degenerate neutrophils

• Lytic necrosis

• Fibrous capsule

GIve a potential aetiological agnt causing chronic suppurative lymphadenitis and its pathogenesis

• Porcine jowl abscess

  • A: Streptococcus porcinus

  • P: Colonises oral cavity/tonsils and spreads to the mandibular lymph nodes

Equine strangles

• Aietiology: Streptococcus equi subsp equi

• Pathogenesis: Inflammation of the URT → abscesses in the mandibular, retropharyngeal and parotid LNs

• May fistulate to surface 

• Can spread to viscera → Bastard strangles 

Caseous lymphadenitis

What are the potential sequelae to equine strangles?

• Can get drainage to the guttural pouches

• Suppurative/ purulent material → Guttural pouch empyema → inspissated (thickened/congealed) material → Chondroid formation

  

What aetiological agent causes caseous lymphadenitis (CLA), how does it differ between species?

• Aeitiology—> Corynebacterium pseudotuberculosis

  • Chronic suppurative lymphadenitis in sheep and goats

  • Ulcerative lymphangitis in horses and cattle

Describe the pathogenesis of caseous lymphadenitis (CLA)

• Usually enters via contamination of shear wounds; rarely by inhalation

• Drains to regional lymph nodes

• Superficial nodes more often affected than internal nodes

  • Prescapular LN /Prefemoral LN

How does CLA present grossly?

Enlargement of LN, as lesion progresses —> characteristic concentric laminations

How does CLA present histologically?

Chronic suppurative (neutrophils) inflammation, caseous necrosis and fibrosis

What are the subclasses of granulomatous lymphadentitis?

Nodular granulomatous lympadenitis

Diffuse granolmatous lymphadenitis

What is the difference in gross presentation between nodular and diffuse granulomatous lymphadenitis?

Nodular:

• Focal or multifocal

• Often white-yellow nodules

• +/- caseous necrosis /mineralisation

Diffuse:

• Enlarged, pale, dry, firm lymph nodes

• Loss of architecture

• Multifocal to coalescing

What aetiological agents can cause nodular granulomatous lymphadenitis?

• Mycobacterium bovis (bovine tb)

• Mycobacterium avium subsp. Paratuberculosis (Johne’s disease)

• Actinobacillus lignieresii (wooden tongue)

• Migrating parasitic larva

What are the potential causes of diffuse granulomatous lymphadenitis?

• Porcine Circovirus type 2

• Histoplasma capsulatum

• Blastomyces dermatitidis

• Cryptococcus neoformans

How does granulomatous lymphadenitis present histologically?

Macrophages, multinucleated giant cells, lymphocytes, plasma cells, fibrosis, necrosis +/- mineralisation

What is the aetiological agent causing bovine TB? How does it present grossly?

Mycobacterium bovis

• Enlargement of the lymph node with single to multiple (multifocal) discrete yellow-tan gritty (caseated) nodules

• Can disseminate to organs

How does bovine TB present histologically?

Granulomas with central necrosis and mineralisation surrounded by epithelioid macrophages and multinucleated giant cells

Lymphocytes + plasma cells

What aetiological agents causes Postweaning multisystemic wasting syndrome (PMWS)?

Porcine circovirus type 2

How does PMWS present grossly?

diffuse enlargement of mesenteric lymph nodes

(wastage of pig on left)

How does PMWS present histologically?

Granulomatous infiltration of the node with large botryoid intracytoplasmic viral inclusions

(botryoid = bunches of grapes appearance)

What can cause lymph node hyperplasia?

Benign reactive hyperplasia

What is the pathogenesis of benign reactive hyperplasia?

• Immunological reaction = response to antigen presentation or circulating interleukin levels

• Causes lymph node enlargement

• Can be localised or generalised

• Lymph nodes draining site of local infection or vaccination

• Also occurs during early stages of lymphadenitis

How does benign reactive hyperplasia present grossly?

• Moderate enlargement of the node(s) = lymphadenopathy

• May bulge on cut section

How does benign reactive hyperplasia present histologically?

• Proliferation of lymphoid follicles with prominent germinal centres

• Increased T cells in the paracortex

• +/ increased plasma cells in the medullary cords

What is being shown here?

Lymph node metastasis

Which tumours are common with lymph node metastasis?

Carcinomas, melanomas, mast cell tumours

How can you stage LN tumour malignancy?

• Stage 0: regional node normal

• Stage 1: regional node enlarged but still freely moveable

• Stage 2: regional node enlarge and fixed

Summary of primary haemotopoietic neoplasias

What can cause lymphoproliferative disease?

• Lymphoma

• Neoplastic disorders of lymphocytes

  • Lymphoid leukaemia —> neoplastic lymphocytes in bone marrow/blood

  • Lymphoma —> neoplastic lymphocytes in tissues/organs

(becomes leukemic when spreads to bloodstream & BM)

How is lymphoma classified?

• Anatomical classification —> multicentric, alimentary, thymic, cutaneous, miscellaneous, leukaemic 

• Biological behaviour —> low grade, intermediate grade, aggressive 

• Cellular morphology —> cell size, nuclear features, mitotic rate 

• Immunophenotype —> B-cell, T-cell, non B/T

What are the clinical signs of lymphoma?

• Nonspecific signs —> Weight loss and loss of appetite

• Painless swelling of 1+ lymph nodes: Lymphadenopathy

• Other signs depend on anatomical location:

  • Retrobulbar lymph node —> exophthalmos

  • Thymic —> dyspnea, oesophageal obstruction

  • Alimentary —> diarrhoea, obstruction or melena

What do enlarged lymph nodes look/feel like grossly?

• Soft to firm, bulge on cut surface, homogenous

• Pale white to tan 

• Immobile

Describe canine lymphoma

• Affects middle aged to older

• Usually medium to high grade

• No known viral association

• Hypercalcaemia of malignancy

What is myelophthisis?

Complete replacement of haematopoietic tissue in BM by neoplasia/fibrosis/other abnormal tissue 

What are the causes of lymphoma?

• Viral infection —> Cats, cattle, mice, chickens

• Hereditary —> porcine

• Unknown (sporadic)

Which types of feline lymphoma are most common vs least common 

1. Alimentary (most common)

2. Multicentric 

3. Thymic

4. Miscallaneous forms (least common)

What is feline lymphoma associated with?

Feline leukemia virus (FeLV)

• Young cats 

• Mediastinal or multicentric form 

What are the forms of bovine lymphoma?

• Enzootic bovine lymphoma (notifiable)

• Sporadic bovine lymphoma

What is enzootic bovine lymphoma?

Multicentric lymphoma of B cell origin —> affects adult cattle esp. dairy

What is the aetiological agent causing enzootic bovine lymphoma?

Bovine leukosis virus (retrovirus)

How is enzootic bovine lymphoma transmitted?

Direct contact, natural breeding, contaminated needles, dehorning and ear-tagging equipment, arthropods

What are the commonly affected sites of enzootic bovine lymphoma?

Lymph node, right atrium, abomasum, spinal canal, uterus, kidney

What are the three forms of sporadic bovine lymphoma? What animals does each effect?

Young animals in the three forms

• Calf form —> <6 months old

• Juvenile form = thymic form —> yearling beef cattle

• Cutaneous form —> 2-3 year old cattle

How does each form of sporadic bovine lymphoma present grossly?

• Calf form —> Symmetrical lymphadenopathy and leukaemia, terminally = BM involvement ± organ infiltration

• Juvenile form —> Mediastinal mass

• Cutaneous —> Plaque like to nodular, round, raised skin lesions

Describe porcine lymphoma

• Multcentric

• Often <1 yo

• More common in F vs M

• Hereditary predisposition in large white pigs

Describe equine lymphoma

• Subcut form in F 

• Alimentary, abdo, splenic & multicentric forms 

Recall the anatomy, structure and function of the thymus

Anatomy

• White to pink, lobulated organ within the anterior mediastinum.

Ruminants and pigs have a large cervical lobe that extends along the cervical trachea.

Structure

• Epithelial tissue and lymphoid tissue

• Lobulated and split into cortical and medullary areas

  

Function

• Proliferation and maturation of T cells

What can causes thymic hypoplasia?

Occurs as part of severe combined immunodeficiencies (SCID) in foals and some breeds of dogs

What can cause thymic involution?

Physiological and age-related change the is gradual and irreversible

What causes thymic atrophy?

Shrinkage of thymic organ by inadequate nutrition, intoxications, infectious agents (e.g. canine distemper virus), lack of antigenic stimuli, drugs etc.

What are the histological changes associated with thymic hypoplasia, involution and atrophy?

All have same histological changes of small numbers of lymphocytes and prominent Hassall’s corpuscles

What are the general features of primary neoplasia of the thymus?

• Space occupying mass in cranial mediastinum

• Dyspnoea

• 2 main differentials

What are the two main differentials of thymus primary neoplasia?

• Thymoma

  • Neoplastic proliferation of epithelial cells

  • Slow growing, encapsulated

  • Dogs, sheep, goats

• Thymic lymphoma

  • Neoplastic proliferation of T-cells

  • Often younger animals (cats, dogs, calves), malignant behaviour

Recall the normal structure and function of the spleen

Anatomy:

• Present in the left cranial part of the abdomen within the greater omentum

• Attached to the greater curvature of the stomach

• Covered by a fibromuscular capsule and dissected by fibromuscular trabeculae

• Varies in size and shape among species

Red pulp

• Structure

  • Sinusoids/vascular spaces

  • Splenic cords

• Function

  • Filters blood- removal of foreign material (phagocytosis)

  • RBC storage

  • Haematopoiesis (EMH)

White pulp

• Structure

  • Periarterial lymphatic sheaths (PALS) (T-cells)

  • Lymphoid nodules (B-cells)

  • Marginal zone (Macrophages)

• Function

  • Immune response

What is splenic amyloidosis?

Usually secondary amyloidosis, chronic inflammation (acute phase protein SAA)

What is the gross presentation of splenic amyloidosis?

 

• Splenomegaly, beige to orange discolouration, waxy to friable appearance

What is the histological presentation of splenic amyloidosis?

• Amorphous eosinophilic deposits often near blood vessels

• Often macrophages and multinucleated giant cells

• Congo red stain- red material turns apple-green under polarised light

What is the pathogenesis of splenic torsion?

• With and without the stomach (gastric dilation and volvulus)

• Twists around the gastrosplenic ligament

How does splenic torsion present grossly?

• Splenomegaly, blue to black, folded back on itself (C or v shaped)

Describe siderotic plaques

• Older dogs, senile changes, poss sequelae to prev. haemorrhage

• Gross —> grey/white, firm encrustation on splenic capsule, usually in margins

• Histo —> contains golden brown pigment (haemosiderin), blue-purple mineralisation

What are the ddxs of haemorrhage on the spleen?

Splenic haematoma, haemangioma and haemangiosarcoma all grossly indistinguishable

What are the potential sequelae to splenic haematoma

• Splenic rupture

• Haemabdomen

• Hypovolamic shock

(indistinguishable from haemangioma & haemangiosarcoma)

What is being shown here?

Accessory spleens

What is being shown here?

Splenic congestion from barbiturate euthanasia —> spleen very enlarged and congested from storage of blood

What are the different inflammatory diseases of the spleen?

• Acute splenitis:

  • Multifocal necrosuppurative splenitis

  • Septicaemia splenitis

• Chronic splenitis

  • Granulomatous splenitis —> nodular, diffuse

What aetiological agents cause multifocal necrosuppurative splenitis?

• Francisella tularensis (Tularemia)

• Yersinia pseudotuberculosis (Yersiniosis)

How does multifocal necrosuppurative splenitis present grossly?

• Multifocal milliary white foci within the spleen.

• Can see similar lesions in the lymph nodes and liver

• Older lesions resemble granulomas/ abscesses

(white dots throughout spleen = areas of necrosis)

What aetiological agents cause septicaemic splenitis?

• African swine fever

• Erysipelas

• Anthrax

How does septicaemic splenitis present grossly?

• Splenomegaly

• Dark discolouration

• Engorged with blood

What aetiological agent causes:

• Nodular granulomatous splenitis

• Diffuse granulomatous splenitis

Nodular granulomatous splenitis —> Mycobacterium avium infection (Mycobacteriosis) in a chicken

Diffuse granulomatous splenitis —> Histoplasma capsulatum (Histoplasmosis) in a dog

When is benign nodular hyperplasia seen?

• In old dogs

• Usually incidental

• May predispose to splenic haematomas

Important to rule out neoplasia

What is the gross and histological presentation of benign nodular hyperplasia?

Gross —> grey to red nodular mass(es)

Histo —> composed of lymphoid tissue and red pulp

What is lymphoid hyperplasia and how does it present grossly?

Hyperplasia of the white pulp

Response to blood-borne antigen/chronic antigenic stimulation

Gross —> lymphoid follicles visible as 1-3 mm foci