Lymphoid Flashcards
List 6 possible responses of the thymus to injury.
Hypoplasia
Atrophy – most common
Haemorrhages/hematoma
Inflammation
Hyperplasia
Neoplasia
Describe thymic hypoplasia.
- Congenital
- Secondary to immunodeficiencies affecting T cells
- Smaller and less populate organs
- Foals and certain dog breeds
How can premature atrophy and physiological involution be distinguished?
Thymus is very large in neonate. Encounters a natural involution after sexual maturity, it can be very difficult to differentiate atrophy from involution. An extremely small thymus in neonatal animals should be considered abnormal
Define atrophy.
Normal when born but then alteration of its cellular density and/or cellular composition and subsequent lobular shrinkage.
What are the causes of thymic atrophy?
- Infectious agents
- Stress – apoptosis of thymic T cells
- Environmental contaminants – mycotoxins, dioxins, PCB, lead, mercury
- Immunotoxicants – anticancer drugs, radiation
- Malnutrition – vitamin B6 or zinc deficiencies causing immunosuppression
Which infectious agents could cause thymic atrophy in cats, dogs, cattle, horses and pigs?
- FIV, FeLV, Parvovirus – cats
- Distemper, Parvovirus – dogs
- Bovine Viral Diarrhoea Virus – cattle
- Equine Herpes Virus 1 – horses
- Classical swine fever virus and PRRS – pigs
What are the causes of thymic haemorrhage or haematoma?
- Thoracic trauma
- Overstretching of the neck
- Rupture of aortic aneurisms
- Neoplasms
- Intoxication with anticoagulant rodenticides
- Spontaneous idiopathic form (young dogs)
Why is inflammation an uncommon cause of thymic lesions?
Usually, viral infections cause destruction of the lymphoid components (lymphocytolysis) and subsequent atrophy rather than an inflammatory response.
What is diffuse thymic hyperplasia?
- Usually observed in calves, rabbits and birds that have been repeatedly immunised or it simply represent a physiological variation.
- Incidental finding
- No clinical signs reported
- Rare or considered accidental
What may follicular thymic hyperplasia be indicative of?
Chronic inflammation or immunologic response.
What are the properties of thymomas?
- Usually benign epithelial cell tumour in goats, cats and dogs in the cranial mediastinum
- Slow growing so occurs in older animals
- Can be cystic, usually appear whiteish
What is the malignant counterpart of a thymoma?
Thymic carcinoma, which is extremely rare.
- Highly invasive
- Most common subtype is the squamous cell carcinoma, common in dogs
In which animals are thymic lymphomas common?
Cats 1-10 years old
Beef cattle 6 to 24 months old
What are the clinical signs of thymus neoplasia?
Clinical signs reflect local compression of the adjacent anatomical structures:
Dyspnoea and oedema due to compression and CVS compromise.
What is the function of spleen trabeculae?
Structural support and contraction for blood expulsion
What is the function of spleen red pulp?
- Erythrocyte storage
- Filtering of old/defective erythrocytes by macrophages
- Filtering of particles and pathogens by macrophages
What is the white pulp of the spleen made up of?
Macrophages
Antigen presenting cells
B and T lymphocytes
What are the causes of splenic atrophy?
- Cachexia due to starvation, malignant neoplastic diseases, malabsorption syndromes
- Chronic radiation
What is senile splenic atrophy?
Common in elderly dogs and horses and is normal
What is the appearance of splenic atrophy?
Small spleen with irregular, pale surface
What are the possible aetiologies of splenic atrophy?
Same as thymic:
- Infectious agents - FIV, FeLV, parvo, distemper, bovine viral diarrhoea virus, EHV1, classical swine fever, PRRS
- Stress - apoptosis of splenic T cells
- Environmental contaminants – mycotoxins, dioxins, PCB, heavy metal (lead, mercury)
- Immunotoxicants – anticancer drugs, radiation
- Malnutrition – vitamin B6 or zinc deficiencies causing immunosuppression
Name 3 examples of splenic overload and infiltration.
Siderotic plaques
Haemosiderosis
Amyloidosis
What are siderotic plaques?
- Incidental finding in old dogs
- Possible link to previous trauma
- Sidero-calcic (iron, calcium ion) impregnation/deposition
- Crusty appearance
What is haemosiderosis?
- Reduced rate of erythropoiesis
- Rapid destruction of erythrocytes due to macrophages
- Pigment is brown/gold
What is amyloidosis?
- Primary or secondary
- Most commonly secondary to chronic inflammation or neoplasia
- Amyloid protein abnormal accumulation
- Organs are yellowish and waxy
What are the splenic vascular changes that can occur?
Hyperaemia/congestion
Infarction
Torsion/volvulus of the spleen
What is active hyperaemia of the spleen?
Increased flow in the organ associated with acute systemic infections and bacterial intoxications, spleen moderately enlarged and can be dark red.
What is passive congestion of the spleen?
- Spleen is very enlarged, black in colour and has lost structure
- Due to disorders in the systemic circulation, administration of barbiturates, haemolytic diseases
What are possible causes of splenic infarction?
Thrombi and thromboembolism – cause vascular damage, hypercoagulative states, endocarditis, septic thrombosis of vena cava
Neoplasia – such as, hyperviscocity syndrome associated to myelomas
Distinguish acute and chronic splenic infarctions.
Acute – dark red, raised, haemorrhagic, demarcated area
Chronic – wedge-shaped, sharply demarcated, grey-white areas
What is the final resolution of splenic infarction?
Fibrous scar
What is torsion/volvulus of the spleen?
Complete twist of the gastrosplenic ligament to splenic vein and artery occlusion (large dog breeds with/without gastric torsion, and pigs).
What does torsion/volvulus of the spleen cause?
Severe congestion and haemorrhagic infarction – bluish in colour due to cyanosis
What are the causes of a splenic rupture?
Primary – trauma
Secondary – splenomegaly, splenic neoplasia, haematomas
What are the possible outcomes of a splenic rupture?
- Haematoma
- Dissemination of small spleen fragments into the omentum (peritoneal splenosis), which is normal
What are the causes of a splenic haematoma?
- Trauma
- Lymphoid hyperplasia nodules
- May also occur from rupture of splenic vascular tumours (haemangioma, haemoangiosarcoma)
What is the risk of splenic haematomas?
May rupture and cause internal haemorrhage
What types of tissue reactions can be caused by splenitis?
Suppurative
Necrotising
Pyogranulomatous
Granulomatous
What is extramedullary haematopoiesis of the spleen?
Response to increased demand for blood cells
What is lymphoid hyperplasia of the spleen?
May be diffuse or follicular, it can be the result of the response to blood-borne antigens (chronic antigenic stimulation)
What is nodular hyperplasia of the spleen?
- Single or multiple nodules
- Mixed cell populations possible but predominantly lymphocytes
- May predispose to splenic haematoma
What neoplasias affects the spleen?
Haemoengiosarcoma – most common neoplasia in dogs
Lymphoma – mast cell tumours, haemangiomas, sarcomas, metastatic tumours (carcinoma, sarcoma)
Why is histology important for splenic neoplasia?
Helps to confirm the nature of the masses as a haematoma, haemangioma and hemangiosarcoma look the same macroscopically.
What causes lymph node atrophy?
- Viral infections (BVD, FIV, Distemper, Feline parvovirus)
- Malnutrition/cachexia
- Old age
- Toxins/chemotherapy/irradiation
What are some examples of lymph node overload and infiltration?
- Pigment
- Fat – mesenteric lymph nodes in pigs, retromammary lymph nodes in cows
- Gas – drainage of emphysematous lesions
- Lymph cysts – accumulation of intra-node lymph due to poor downstream drainage
What does yellow pigment of lymph nodes indicate?
Jaundice
What does dark red/brown pigment of lymph nodes indicate?
- Haemosiderin
- Haemorrhage/prolonged stasis
- Iron-injected piglet
- Melanin
What does black pigment of lymph nodes indicate?
Melanin (normal, particularly in pig lymph nodes)
What can lymph node hyperplasia be caused by?
Lymphadenomegaly – lymph node enlargement. Localised or generalised, peripheral or internal
Reactive – response to antigenic stimuli. Benign, transient, local or systemic
What is the disease, species and exudate of corynebacterium psuedotuberculosis?
Caseous lymphadenitis
Ovine
Caseous-suppurative
What is the disease, species and exudate of streptococcus equi?
Strangles
Horse
Suppurative
What is the disease, species and exudate of streptococcus porcinus?
Jowl abscess
Pig
Suppurative
What is the disease, species and exudate of porcine circovirus-2?
PCV-AD
Pig
Granulomatous
What is the disease, species and exudate of mycobacterium bovis?
TB
Bovine
Granulomatous
What is the disease, species and exudate of mycobacterium avium partuberculosis?
Johne’s disease
Ruminants
Granulomatous
What is the disease, species and exudate of feline coronavirus?
Feline infectious peritonitis
Cat
Granulomatous
What is the disease, species and exudate of rhodococcus equi?
Rhodococcosis
Horse
Pyogranulomatous
Describe the pathogenesis of lymphadenitis caused by equine strangles.
- Bacterium inhaled/ingested
- Attach to tonsils, penetrates deeper
- Drain into lymphatic vessels and regional lymph nodes
- Large abscesses leading to pharyngeal compression, respiratory stridor and dysphagia
- Rupture
- Discharge to skin surface, spread medially into pouches leading to reservoir and carrier state
- Spread via blood or lymph to other organs
Describe the pathogenesis of caseous lymphadenitis with corynebacterium psudeotuberculosis.
- Wound infection
- Drain into local lymph nodes
- Suppurative inflammation
- Abscesses form
- Abscesses are encapsulated
- Capsule is compromised, causing bacteria to escape
- Alternating necrosis, pus formation and reformation of the capsule
- Drain externally through the skin and/or spread to other organs via lymph/bloodstream
Describe granulomatous lymphadenitis with bovine tuberculosis.
- Inhalation of aerosol droplets
- Central caseous necrosis containing macrophages with mycobacteria. With/without necrosis and mineralisation
- Halo of epithelioid and foamy macrophages and multinucleated giant cells
- Outer layer of lymphocytes
- Fibrous capsule
How can lymphatic vessels lead to lymph node lesions?
- Lymphangitis (inflammation of lymphatics)
- Lymphangiectasia (enlargement of vessels)
- Lymphoedema (accumulation of fluid)
- Lymphatic rupture - neoplasia, inflammation, trauma
What does rupture of the thoracic duct cause?
Chylothorax
What is lymphoma?
Neoplastic lymphoid cells arising in lymph nodes and/or extranodal locations.
What is leukaemia?
Neoplastic hematopoietic cells arising usually in the bone marrow
What is multicentric lymphoma?
- Frequently widespread in the body, in particular spleen and liver are commonly involved
- 80% of all cases in dogs, common in cattle, horses, ruminants, pigs
What type of cell typically cutaneous lymphoma?
T cell
Distinguish epitheliotropic and non-epitheliotropic cutaneous cell lymphomas.
Epitheliotropic - mycosis fungoides/Sezary syndrome
Non-epitheliotropic - appear as a subcutaneous ‘panniculitis like’ T cell lymphoma or anaplastic large T cell lymphoma
What is mycosis fungoides cutaneous lymphoma?
- CD8+ T cell)
- Older dogs, cats, horses
- Chronic multifocal – skin, mucous membranes, mucocutaneous junctions
Distinguish mycosis fungoides and sezary syndrome.
MF: diffuse erythema, scaling, focal hypopigmentation, plaques and nodules
SS: initially limited to skin and then later lymphadenopathy, leukaemia and internal organs affected
What type of cell is typically involved with alimentary/intestinal lymphoma?
B cells
Describe the pathogenesis of alimentary/intestinal lymphoma.
- Originates at any level of the GI tract
- Spread through mesenteric lymph nodes
- Solitary or multiple nodules, sometimes diffuse involvement of an intestinal segment/thickening of intestinal wall
What can alimentary/intestinal lymphoma lead to?
- Malabsorption and weight loss may be present
- Metastasis to mesenteric lymph nodes and other viscera
What are 2 examples of viral aetiology lymphomas?
Feline leukaemia virus
Bovine leukaemia virus/enzootic bovine mutagenesis
Describe how FLV causes lymphoma.
- Neoplastic transformation caused by insertional mutagenesis
- Insertion is random so not every infected cat will develop lymphoma
- Common T cell lymphoblastic lymphoma but possible also B cell lymphoma
- Spread horizontally among cats
How does BLV cause lymphoma?
- Carriers additional genes that encode for regulatory and accessory proteins
- Transmission occurs horizontally by transfer of infected lymphocytes
- Diffuse large B cell lymphoma
- Development of antibodies against the viral antigens leads to asymptomatic stage to lymphocytosis and eventual neoplasia.
What is Marek’s disease?
A lymphomatous and neuropathic disease of domestic fowls caused by a herpesvirus
What are the clinical signs observed with Marek’s disease?
Paralysis of the legs and wings. Grossly can be observed enlargement of peripheral nerves.
Where can lymphomatous lesions develop in Marek’s disease?
Multiple organs such as the ovary, liver, spleen , kidneys, lungs, heart, proventriculus and skin.
What is sporadic lymphoma (non-BLV)?
- Calf/juvenile form is usually multicentric
- Commonly 3 months to 6 months, may be present at birth
- Symmetrical lymphadenopathy and leukaemia
How can lymphoma be anatomically classified?
Multicentric
Solitary
Thymic
Alimentary
Cutaneous
How can lymphoma be cytologically classified?
- Small to large cells
- Well differentiated to anaplastic
- Cytoplasm – amount, type, nucleus:cytoplasm ratio
- Nuclear size, shape, chromatin and nucleoli
- Mitoses (more mitosis is bad)
How are lymphomas histologically classified?
Follicular (nodular) – cells organised in distinctive nodules
Diffuse – sheet of cells
How are lymphomas classified by immunophenotype?
- T or B cell
- Non T non B (NK)
- T cell rich B cell lymphoma
- B cell rich T cell lymphoma
How are T cell lymphomas identified by molecular markers?
Positive to CD3
Negative to CD20, CD79a, Pax5
How are B cell lymphomas identified by molecular markers?
Positive for CD20, CD79a, Pax5
Negative CD3
How are non T non B cell lymphomas identified by molecular markers?
Negative for CD3, CD20, CD79a and Pax5
How are B cell rich T cell lymphomas identified by molecular markers?
Positive for CD3 due to neoplastic cells
Positive for CD20, CD79a, Pax5 due to infiltrating inflammatory or local cells
How are T cell rich B cell lymphomas identified by molecular markers?
Positive for CD3 cells due to infiltrating inflammatory or normal local cells
Positive for CD20, CD79a, Pax5 due to neoplastic cells
What is positivity and negativity of molecular markers determined by?
By the staining, the depth of which is determined by how positive/negative it is.
What is antigen receptor rearrangements?
Clonality assay that helps to distinguish neoplastic from inflammatory lymphoid cells when the morphological, cytological or immunophenotypic properties of a lymphoid cell population are inconclusive.
How are T and B cell lymphomas distinguished on an antigen, receptor rearrangements?
Suspect T cell lymphoma – PCR targets the CDR3 region of the T cell receptor gamma
Suspect B cell lymphoma – PCR targets the immunoglobulin heavy chain genes
