Leukaemia and lymphadenopathy Flashcards
Leukaemia, lymphoma, lymphadenopathy, pathology of the lymphoid system
Define leukaemia
Neoplastic condition of bone marrow where neoplastic cells of lymphoid or non-lymphoid stem cells or their progeny, undergo clonal expansion with or without cellular differentiation
What causes the clinical signs seen with leukaemia?
- Failure of normal marrow function
- Infiltrated organ dysfunction
- Hyperviscosity (increased globulin production)
- Paraneoplastic syndromes (IMHA, hypercalcaemia
What are the 3 types of leukaemic proliferative disorders?
- Lymphoproliferative
- Myeloproliferative
- Myelodysplastic
What are the categories of lymphoproliferative disorders?
- Neoplastic B, T or NK cells: lymphoma, lymphoid leukaemia
- Plasma cell neoplasia: Myeloma
What are the categories of myeloproliferative disorders?
- Erythroid
- granulocytic monocytic
- Megakaryocytic
Give examples of erythroid myeloproliferative disorders
- Erythroleuakemia
- Erythemic myelosis
- Polycythaemia ver
Give examples of granulocytic-monocytic myeloproliferative disorders
- Myeloblastic leukaemia
- Myelomonocytic
- Monocytic
- Eosinophilic
Give examples of megakarycytic myeloproliferative disorders
- Megakaryoblastic
- Thrombocythaemia
What is a lymphoma?
Proliferative disorder arising in organ or lymph node
What is lymphoid leukaemia?
Proliferative disorder arising in bone marrow/blood
What is a myeloma?
Plasma cell neoplasia in the bone marrow, produces antibodies
What cells type are myelomonocytic myeloproliferative disorders affecting?
Common precursor for myeloid cells and monocytes
What are myelodysplastic proliferative disorders?
Neoplasia in bone marrow, but is not as obvious what type as cells are not released into the circulation
Describe aleukaemic proliferative disorders
- Do not have high white cell count
- bone marrow full of neoplastic white cells, damaged white cell production
- Unable to exit into circulation due to abnormality
How does cytopaenia develop with myeloid and lymphoid proliferative disorders?
- Bone marrow crowded by neoplastic cells
- stops production of other cell types
- Low white cell count in blood, but those seen will be abnormal
- Lose neutrophils first, then platelets then RBCs
Why does it take time for the number of RBCs in the blood to drop in myeloid or lyphoid proliferative disorders?
RBCs live for ~100 days
Describe the characteristics of acute lymphoid or myeloid leukaemias
- Neoplastic transformation during stem cell proliferation
- Large numbers of immature (undifferentiated) cells
- Aggressive rapid disease
- Cytopaenia very common
How is the acute leukaemia type diagnosed?
- Can be acute lymphoid or acute myeloid
- Diagnosis by immunophenotyping or clonality testing
- Bone marrow aspirate and viewing under microscope often wrong
Which type of acute leukaemia is more common?
Acute lymphoid leukaemia more common
What is leukaemia defined as based on the proportion of neoplastic blast cells in marrow?
> 30% = leukaemia
Outline the methods of immunophenotyping used for acute leukaemias
- Immuno-cytology/histology of marrow aspirates or biopsies
- Immuno-labelled flow cytometry of EDTA blood or marrow
Outline the method for clonality testing for acute leukaemias
- PCR for Antigen Receptor Rearrangements (PARR)
- Molecular biology looking at DNA of the lymphocyte, specifically the antigen receptor
- Entire population carrying same antigen receptor = more likely to be neoplastic
- Reactive population = multiple receptor types
describe the characteristic of chronic leukaemias
- Neoplastic transformation after differentiation
- Leads to large numbers of mature (differentiated) cells
- Less organ damage, normal cells but more than normal
- Slow progression, less aggressive
- Cytopaenia rare
Describe chronic lymphoid leukaemia
- Easy to identify
- Increased number indicates chronic
Describe chronic myeloid leukaemia
- More difficult to identify
- Increased numbers may be due to chronic inflammatory condition e.g. abscess
- Bone marrow aspirates to identify neoplastic cells in bone marrow
Compare the proportion of blast cells in marrow in lymphoma involving the bone marrow and acute lymphoblastic leukaemia
- Lymphoma: <40% in marrow
- Leukaemia: >40% in marrow
Compare the circulating blast count in lymphoma involving the bone marrow and acute lymphoblastic leukaemia
- Lymphoma: lower
- Leukaemia: higher
Compare the cytopaenia in lymphoma involving the bone marrow and acute lymphoblastic leukaemia
- Lymphoma: mild or absent
- Leukaemia: severe
Compare the lymphadenopathy in lymphoma involving the bone marrow and acute lymphoblastic leukaemia
- Lymphoma: massive
- Leukaemia: mild to moderate
Compare the systemic illness lymphoma involving the bone marrow and acute lymphoblastic leukaemia
- Lymphoma: may not be systemically ill
- Leukaemia: usually systemically ill
What are the potential causes of lymphadenopathy?
- Reactive hyperplasia
- Lymphadenitis
- Metastatic neoplasia
- Lymphoma
How can the cause of lymphadenopathy be identified?
FNA/FNCS
- NB before steroids (kill lymphocytes)
Compare the appearance of small, medium and large lymphocytes
- Small: very thin rim of cytoplasm, only slightly larger than erythrocytes
- Medium: distinctly larger than erythrocyte,s, larger rim of cytoplasm seen
- Large: much larger than erythrocytes, large rum of cytoplasm
Describe the cytological appearance of reactive hyperplasia of the lymph node
- Indistinguishable from normal
- Heterogenous cell population
- Marjority 75-95% small lymphocytes
- low stage medium and large cells (up to 15% in reactive)
- Occasionally plasma cells
- Occasionally macrophages (>2% in reactive)
- Very few neutrophils, eosinophils, mast cells
Describe the cytological appearance of a lymph node with lymphadenitis
- Inflammatory process in the lymph node itself i.e. lymph node is target of insult
- Increased neutrophils (>5%) or eosinophils (>3%)
- Macrophages (>3%) incl epitheloid and multinnucleate giant cells in granulomatous inflammation
- Inflammatory cells may be mildly increased or completely replace normal structure
What does eosinophilic lymphadenitis suggest?
Allergy
What does granulomatous or pyogranulomatous lymphadenitis suggest?
Fungal or protozoal infection
What may be found on cytology in lymph enlargement as a result of metastatic neoplasia?
- Carcinoma cells drained into lymph node
- Myeloproliferative disorders
- Mast cells (>3%)
- Melanoma cells
Describe the cytological appearance of the lymph node with lymphoma
- Increased % of large immature lymphocytes (confident at 50% either medium or large type in population)
- More mitotic elements than seen in reactive
- More tingible body macrophages
- More lymphoglandular bodies (cell fragility)
What is the role of the spleen?
- Removal and destruciton of erythrocytes by histiocytes (non-specific removal of effete, damage, abnormal RBCs, specific removal of Ab coated RBCs)
- Retrieval of iron from erythrocyte breakdown
- Storage of blood
Describe the histological appearance of the spleen
- Red pulp makes up majority (purple), meshwork of sinusoids with blood and macrophages
- White pulp: lighter/blue, mainly T/B lymphocytes
Give examples of common incidental findings on histology of the spleen
- Senile nodular hyperplasia
- Congestion
- Siderofiborisis/calcinosis
- Surface indentations
Describe the histological apperance senile nodular hyperplasia of the spleen
- Mixture of red and white pulp tissue
- Possibly coincidental haemorrhage
- If found on ultrasound, FNA, examine on slide and send to ClinPath before removal of spleen or euthanasia
How does senile nodular hyperplasia occur?
Some areas do not work well with age, so others pick up the slack and compensate
Describe the gross appearance of splenic congestion
When cut open, blood will ooze out
How does siderofibrosis/calcinosis of the spleen occur?
- massive haemoglobin iron turnover in spleen
- Over time can lead to accumulations of calcified iron storage leading to fibrosis
How do surface indentations of the spleen occur?
Normal variation, no clinical relevance
List the potential responses of the spleen to injury
- Acute inflammation
- Hyperplasia of monocyte/macrophage system: granulomatous disease
- Lymphoid atrophy
- Storage of blood or contraction to expel reserve blood
- Neoplasia
Describe the appearance of acute inflammation of the spleen
- Hyperaemia
- Microabscesses, abscesses
- Swells
- Dilation of vascular structures
Describe the appearance of hyperplasia of monocyte/macrophage system in the spleen, and give examples of causes
- Granulomatous disease
- May be mycobacterial, fungal, porcine circovirus infecction
- Chronic condition where macropahges are “losing” against the infectious agent
Describe the processes taking place with hyperplasia of the lymphoid system in the spleen and common causes
- Production of plasma cells and antibody
- Cell mediated immunity
- Often viral infection
Describe the cause of and appearance of lymphoid atrophy of the spleen
- Viral infection affects lymphocytes directly, leading to loss of lymphocyte population
- If occurs over a prolonged period of time, lose lymphocytes and end up with loss of white pulp = lymphoid atrophy
- Need to investigate for viruses that affect lymphocytes e.g. parvovirus, distemer
What are the 2 types of splenomegaly?
- Diffuse (uniform)
- Focal to multifocal (nodular)
What are the potential causes of diffuse splenomegaly?
- Infection/reactive hyperplasia
- Congestion
- Neoplasia (leukaemia, systemic tumours e.g. mast cells, haemangiosarcoma, myeloma, lymphoma)
- Haemolytic anaemia
- Advanced amyloidosis
Outline the potential causes of splenic congestion
- Barbiturate euthanasia
- Anthrax
- Torsion/GDV (occludes splenic vein, artery continues to supply blood, may rupture leading to death)
List the potential causes of focal to multifocal splenomegaly
- Nodular hyperplasia
- Focal haematoma
- Hamengioma/sarcoma, leiomyoma/sarcoma, fibrosarcoma
- Abscesses e.g. Rhodococcus, Corynebacterium
In a case of haemolytic anaemia, the spleen is small and the bilirubinis high. Does this suggest intra or extravascular haemolytic anaemia
Intravascular
In a case of haemolytic anaemia, the spleen is enlarged. Does this suggest intra or extravascular haemolytic anaemia? Explain why
Extravascular, due to proliferation of macrophages leading to enlargement of the spleen
What does the appearance of a “milky” spleen indicate?
Proliferation of cells
Describe follicular hyperplasia of the spleen (appearance, cause)
- Reactive hyperplasia of white pulp lymphoid tissue
- Multiple white nodules indicating reactive spleen, proliferation of T and B cells due to detection of pathogen in blood
- Suspicious of viraemia if see this
List the different presentations of splenic inflammation
- Can be capsule/peritonitis
- Parenchyma: splenitis or splenic abscesses
What is the main concern regarding splenic haemorrhage?
Will affect the whole system and can be fatal quickly
Describe splenic haemangiosarcomas as a cause of splenic haemorrhage
- Omentalised spleen
- Bleeds through
- Underneath is malignant tumour that started in blood vessels of spleen
- Prone to rupture
Describe splenic haemangiomas as a cause of splenic haemorrhage
- Benign vascular umours
- May rupture and be fatal e.g. if rupture too big to clot and close lesion
Describe the gross appearance of splenic rupture
If animal survives, may get formation of accessory splenic tissue
Describe haematomas as a cause of splenic haemorrhage
Can rupture, but not usually life threatening as tend to be small, but is not always the case
Describe the gross appearance of splenic lymphoma
- Massively enlarged spleen
- Uniform enlargement, with white area of lymphoid proliferation
- White shiny lesions, more nodular
- Multiple variable size tumour emboli in the spleen
Describe the histopathological appearance of a haemangiosarcoma
Full of blood, create a lot of poor vascular channels that can be seen as spaces on histology - may cause damage to RBCs, show up as schistocytes on smears
Describe the development and spread of haemangiosarcomas
- Metastasise early, quickly and widely
- Focal proliferation
- Can start anywhere in the circulatory system
Describe the normal histological appearance of the thymus
- Cell dense cortex
- Full of immature T cells
- Can see thymus and medulla clearly
List the potential responses of the thymus to injury
- Lymphoid atrophy
- Inflammation (very rare)
- Haemorrhages and haematomas
- Neoplasia
How does thymal injury lead to lymphoid atrophy?
No thymus tissue = no maturation of T lymphocytes
Give examples of causes of thymal inflammation and describe the appearance
- Porcine circovirus, Rickettsial infection
- Neutrophils and hyperaemia
How may thymal haemorrhages and haematomas occur?
May occur during seizure/shock
List the potential diseases processes that may occur in the thymus
- Cyst formation
- Hypoplasia
- Atrophy
- Depletion
- Neoplasia
Describe thymal cysts
- Involution during puberty and some remnants remain producing cysts
- Generally do not cause a problem
Describe thymal hypoplasia
- Causes immunodeficiency
- Genetic condition
- Cannot differentiate between self and non-self
- No T cels produced
Describe thymal atrophy
- Can be stress induced or age related (normal physiological involution)
- Age related is due to lack of growth factors and proliferative cytokines, accelerated by stress
How does thymal depletion occur?
Viral infection e.g. EHV-1, FPV, CPV, CDV, FIV
Give examples of thymal neoplasms
- Thymic lymphoma (cats and cattle)
- Thymoma
Describe thymomas
- Epithelial plus lymphoid cells
- Some association with myasthenia gravis suggested
- Usually benign proliferation of all structures within the thymus, including the epithelial structures e.g. Hassle’s corpuscles
What is SCID and how does it develop?
- Not single condition, collection of entities varying in severity and molecular basis
- All result in failed production of functional lymphocytes (splenic and thymic hypoplasia)
Which species are classically affected by SCID?
Horses, humans, mice, dogs
Describe SCID in Arabian horses
- Autosomal recessive in Arabian horse and their crosses
- All affected foals die by 5mo as a result of infection by variety of pathogens
E.g. Equine adenovirus, Pneumosystitis carinii, Cryptosporidium parvum, rhodococcus equi
Describe the lesions seen in foals with SCID
- Bilateral cranioventral bronchopneumonia
- Small spleen, lymph nodes and thymus
- Abscesses common
How is SCID diagnosed in horses?
PCR to identify genetic condition
What are the 2 major molecular mechanisms of SCID of importance in animals?
- Autosomal recessive defect causing inhibition of DNA dependent protein kinase (Arabian foals, JRT, strain of mice)
- X-linked defect in type I cytokine receptors (Bassett hound, Cardigan Welsh Corgi)
Give examples of myeloid neoplasias
- Myeloid leukaemias/dysplasias
- Histiocytic neoplasias
- Mast cell tumours
Name the anatomical distributions that are possible for lymphomas
- Multicentric (most common, multiple organs affected)
- Alimentary
- Medastinal
- Other e.g. cutaneous, cardiac
- Ontra and extradural primary lymphoma
Describe the metastasis of lymphomas
- Local lymph nodes similarly affected as primary tissue leading to lymphadenomegaly
- Infiltration of liver and spleen common
- Spread haematogenously
What may lymphomas occur secondary to?
Viral infection e.g. FeLV, BLV, bovine enzootic lymphoma
- BLV often abomasal involvement
What is the prognosis for lymphomas dependent on?
- Immunophenotype (B or T cell or non-B/non-T)
- Cellular morphology
- Histologic pattern (diffuse vs follicular)
- Biologic behaviour (low to high grade)
Describe the characteristics of a high grade lymphoma
- Neoplastic lymphocytes large
- Large nuclei with dispersed chromatin and prominent nuclei
- Mitosis figures evident
- Lots of variability in cells and nuclei
- Quick, wide, easy metastasis
Describe the characteristics of a low grade lymphoma
- Neoplastic lymphocytes small to intermediate size
- Partially condensed chromatin
- Look like normal mature lymphocytes mostly
What structures are commonly affected by lymphoma in cattle?
- Abomasum
- Vertebral canal
- Kidney
- Heart
- Retro-orbital space
- Uterus
What structure is usually affected by alimentary lymphomas?
Small intestine
Describe the gross appearance of splenic lymphoma
- Gross enlargement with pale subscapular nodules
- mottled appearance of spleen due to infiltration of malignant lymphocytes into portal areas
Describe the histopathological appearance of splenic lymphoma
- Sheets of round cells effacing normal splenic architecture
- Absence of normal red or white pulp
What is meant by a blast crisis?
Sudden switch from chronic to acute leukaemia, unknown cause
Describe the bone marrow in a case of chronic leukaemia
- Hypercellular bone marrow
- Consists entirely of haematopoietic tissue (red), no fat
