Pathology of the Hematopoietic System Pt 1 Flashcards
What are the primary lymphoid organs?
Thymus
Bursa
Peyers patches
Bone Marrow
What are the secondary lymphoid organs?
Tonsils
Spleen
Lymph nodes
Peyers patches
Bone Marrow
What occurs in the primary lymphoid organs?
Lymphocyte development
What occurs in the secondary lymphoid organs?
Lymphocyte antigen response site
What are the sources of lymphocytes and how that changes as time goes on?
Yolk Sac -> fetal liver -> bone marrow
What is the routes of lymphocytes from development to antigen response?
Source ( yolk, fetal liver, bone marrow ) -> Primary lymphoid organs -> secondary lymphoid organs
Where does hematopoiesis occur? Is that the same throughout life? What changes as the animal ages? What bones in adults?
- The composition of the marrow changes with age.
- Hematopoiesis occurs throughout flat and long bones.
- Hematopoietic tissue (red marrow) regresses and is replaced with nonhematopoietic tissue, mainly fat (yellow marrow).
- In adults, hematopoiesis occurs primarily in the pelvis, sternum, ribs, vertebrae, and proximal humerus and femur.
What is erythropoiesis? What stimulates it?
- Erythropoietin (Epo) regulates production of RBCs
- Release of Epo stimulated by hypoxia
- Other stimulators: ILs, CSFs, hormones
What is the stages of RBC development?
What are myeloid cells?
Granulocytic and monocytic cells are referred to collectively as myeloid cells.
What is the function of neutrophils and monocyte derived macrophages?
Neutrophils and monocyte-derived macrophages: phagocytosis and microbicidal activity
What is the function of eosinophils and basophils?
- Eosinophils and basophils: parasiticidal activity, allergic reactions
What is the function of macrophages?
Macrophages: antigen processing and presentation, and cytokine production
What are the stimulators of granulopoiesis and monocytopoiesis?
- Stimulators of granulopoiesis and monocytopoiesis
- Interleukins (ILs)
- Granulocyte colony-stimulating factor (G-CSF) and GM (granulocyte-macrophage)-CSF
What regulates thrombopoiesis? What is another name for this?
- Thrombopoietin (Tpo), synthesized primarily in the liver, regulates thrombopoiesis.
- Megakaryopoiesis
What are the stages of megakaryopoiesis?
What other cells can be found in the bone marrow?
- Lymphocytes (1-10%)
- Plasma cells (<1%)
- Stromal cells: reticular cells, adventitial cells, adipocytes * Osteoblasts, osteoclasts
When should you submit bone marrow aspirates/ core biopsies? What should you submit at the same time?
When?
* Any abnormal hematology finding such as:
* Unexplained cytopenias (any non-regenerative anemia)
* Maturation defects or morphologic abnormalities in blood cells * Potential myeloproliferative/ lymphoproliferative disease
* Potential malignancies metastatic to the bone marrow
- Must submit a concurrent CBC!
How do you obtain bone marrow aspirates and core biopsies?
How?
* Located in multiple sites but responds as a single tissue
* Samples can be taken from any bone with red marrow:
* Proximal femur, iliac crest, proximal humerus of dogs and cats * Sternum of horses
* Proximal rib of cattle
* Aspirates and core biopsies
What is the diagnostic occurring in this image?
bone marrow aspirates and core biopsies
What is the importance of bone marrow aspirates/ smears?
- Interpreted by clinical pathologists
Important for: - Cellular morphology and maturation
- Erythroid to myeloid ratio (M:E ratio)
- Primary or metastatic neoplasia
What is the importance of bone marrow core biopsies?
- Interpreted by anatomic pathologists
Important for: - Ratio of fat to hematopoietic cells
- Erythroid to myeloid ratio (M:E ratio)
- Adequacy of iron
- Stromal elements (e.g. for myelofibrosis)
- Primary or metastatic neoplasia
What diagnostic is seen here?
Bone marrow aspirate/smears
What diagnostic is seen here?
Bone Marrow Core biopsy
What is this image of?
histopath of bone marrow core biopsy
What does each color represent in this image?
Teal: polychromatophilic rubricytes
Purple: Metarubricyte
Pink: Progranulocyte
Orange: Rubriblasts
Green: Mature Neutrophil
What is the normal myeloid/ erythroid ratio?
~ 3: 1
How can you tell if you have an abnormal ratio if there is too many erythroid cells vs. too few myeloid cells.
THIS IS WHERE CBC IS IMPORTANT.
Is this cats bone marrow core biopsy normal?
What are the possible bone marrow patterns that can be seen?
Bone marrow patterns
* Hyperplasia
* Hypoplasia
* Myelitis/Necrosis
* Dysplasia/Neoplasia
* Myelofibrosis
What is important to note about hyperplasticity of bone marrow cells?
- One or multiple cell lines may be hyperplastic
depending on the stimulus
What are the stimuli for Erythroid Hyperplasia and Megakaryocytic Hyperplasia?
- Erythroid hyperplasia ➝ response to anemia
- Megakaryocytic hyperplasia ➝ response to ↓
platelets
What is the stimuli for the different cells in myeloid hyperplasia?
- Myeloid hyperplasia (monocytic/granulocytic cell
lines) - Neutrophilia ➝ bacterial infections, tissue necrosis
- Eosinophilia ➝ parasites, hypersensitivities
- Monocytosis ➝ chronic infections, specific agents
What is the pathogenesis of hyperplasia of cells in the marrow?
- Pathogenesis:
- ↓cell numbers in blood caused by increased
peripheral demand; or adequate numbers of hypofunctional cells in peripheral blood lead to ↑cell production in the marrow in response to poietins and interleukins.
What is occurring in this image?
What is bone marrow hypoplasia/ atrophy? What can be seen with this? What is the sequel dependent on?
- Decreased proliferative activity * Usually characterized by increase in yellow marrow * Often accompanies marrow degeneration. * Sequel will depend on cell line(s) affected
What are some examples of bone marrow hypoplasia/ atrophy?
- Anemia of chronic disease or inflammation
- Immune-mediated
- Cytotoxic or drug-induced
- Infection: Parvovirus, FeLV, FIV
- Endocrine-induced
- Iron deficiency
- Renal failure (EPO decreased)
- Malnutrition
- Inherited disorders
- Idiopathic
FELV, FIV, Parvo -> can infect proginator cells and affect the ability to regenerate these cells.
What can you see in this image?How would you describe the gross lesion? What is the likely cause?
What is myelitis and bone marrow necrosis? What are some common cause?
Inflammation
* Neutrophilic, granulomatous or pyogranulomatous
Necrosis:
* Neoplasia
* Infections
* Sepsis
* Drugs
* Toxins
* Radiation
What can be seen in this image?
What is myelodysplastic syndrome? What is it characterized by? What does it usually precede? What is an example of a condition that can cause this?
Myelodysplastic syndrome (MDS)
* A group of clonal myeloid proliferative disorders with ineffective hematopoiesis in the bone marrow
* Characterized by ineffective hematopoiesis
* Can precede acute myeloid leukemia
* Typically there is a peripheral cytopenia of one or more cell lines and concomitant marrow hypercellularity.
* FeLV infection
* alot of cells in bone marrow undergo apoptosis very quickly so you still see peripheral cytopenia.
What is myelofibrosis?
- Inappropriate fibroblast proliferation of the medullary spaces with replacement of hematopoietic tissue.
- Due to bone marrow injury with cytokine dysregulation
- Cytopenia
What is occuring in this image?
myelofibrosis
What are the categories of hemopoietic neoplasias?
What are the subcategories of lymph-proliferative disease?
What are the subcategories of myeloproliferative disease?
What are leukemias?
What are the types of acute leukemias?
- Acute myeloid
- Acute undifferentiated or mixed phenotype
- Acute lymphoid
What are the types of chronic leukemias?
- Chronic myeloid
- Chronic Lymphoid
What is likely occurring in this dog?
What is lymphoma? What are the causes? What are they classified by under the World Health Organization ?
- One of the most common malignant neoplasms in
domestic animals. * Can be idiopathic (sporadic) or due to viral infections:
mice (M u LV ), cats (FeLV) and cattle (BLV). - Current WHO classification of canine lymphomas
- Histological Pattern, Nuclear size (compared to RBC), Mitotic Rate per 400x HPF, Immunophenotype.
What is the histological patterns of lymphoma?
nodular or diffuse
What is the nuclear sizes of lymphoma compared to RBCs?
Small
Intermediate
Large
What is the mitotic rate per 400x HPF for lymphoma?
What are the immunophenotypes for lymphoma?
B Cell
T Cell
What is the IHC looking for for T cell lymphoma?
CD3
What is the IHC looking for for B cell lymphoma?
B cells: CD20, Pax5, CD79a
What is PAAR used for in terms of immunophenotyping for lymphoma?
What are the clinical signs of lymphoma?
Clinical signs of lymphoma
* Non-specific clinical signs: weight loss and anorexia
* Enlargement of multiple lymph node
* Other signs depend on anatomic location:
* Retrobulbar lymph nodes➝ exophthalmos
* Thymus ➝ dyspnea, esophageal obstruction
* Alimentary ➝ diarrhea, obstruction or melena
What are gross lesions seen of lymphoma in animals?
What is seen in this image?
What is seen in this image?
What is seen in this image?
What is seen in these cytologies?
What is canine lymphoma? What animals does it typically effect? What is the typical type of lymphoma seen? What is the typical grade seen? What other changes can be seen ?
What percent of dogs with lymphoma have multicentric lymphoma?
85%
What causes hypercalcemia of malignancy?
- Hypercalcemia of malignancy is
occasionally seen in dogs with
lymphoma → secretion of PTHrP
What is feline lymphoma? Which kind is more frequent? What is the order of type of feline lymphoma from most to least frequently Seen?
- Most common malignant neoplasm of cats * Alimentary > multicentric > thymic > miscellaneous forms
What viral association is seen for feline lymphoma?
- Association with feline leukemia virus (FeLV):
- 10 -20 % of cats with lymphoma are FeLV+
- FeLV is associated with mediastinal and multicentric T cell lymphoma
- Young cats!
What is commonly seen in cats with lymphoma?
- Leukemia and bone marrow involvement are common
What is the order of most to least common types of lymphoma in cats?
- Alimentary > multicentric > thymic > miscellaneous forms
What is seen in this image?
Thymic lymphoma in cats
What is gastrointestinal lymphoma? What are the types? Who is each more common in?
Enteropathy-associated T cell lymphoma (EATL) * Type 1 (large cell) – most common in dogs
* Type 2 (small cell) – most common in cats
* Arises from the diffuse MALT of the small intestine
* Median survival time of 29 months
* Difficulty in diagnosis, especially in endoscopic samples
* IHC and PARR
What is seen in these images?
you can see alot of lymphocytes packed in the villi and the mucosa. This is indicative of enteropathic t cell type 2 lymphoma.
What is bovine lymphoma? What are the types?
BLV associated lymphoma (enzootic bovine leukosis)
and
Non BLV lymphoma (sporadic form) most often T cell lymphoma
What is BLV associated lymphoma? What percent of cows with BLV develop lymphoma? What are typical areas in the body affected? What age does it most frequently occur in?
What is non blv lymphoma? What are the types and when do they typically occur?
What is the likely causes of the lesions seen in these images?
What can be seen in this image of a cow?
Cutaneous lymphoma in a cow
What is multiple myeloma? What is the pathogenesis of this?
- Malignant tumor of plasma cell origin
arising in the bone marrow - Neoplastic (clonal) plasma cells secrete
immunoglobulin leading to hypergammaglobulinemia
What is the specific diagnostic criteria for multiple myeloma?
- Specific diagnostic criteria
- Neoplastic plasma cells in the bone marrow
- Lytic bone lesions
- Presence of clonal immunoglobulin
paraproteins in the serum (monoclonal
gammopathy) or urine (Bence-Jones protein)
What is the gross pathological lesions seen with multiple myeloma?
- Gross: Pale pink to dark red gelatinous masses replace bone marrow – typically multiple masses
What can see histologically with multiple myelomas?
Sheets of neoplastic plasma cells
What is a likely diagnosis based on these images?
What percentage of cows with BLV develop lymphoma?
- Approximately 1-5% of BLV-infected cattle develop B cell leukemia/lymphoma.
What is seen in this image being indicated by the green arrows?
Neoplastic lymphocytes
What are the 2 most important diagnostics for lymphoma?
IHC and PARR
What is PARR used for when diagnosing lymphoma?
We use this to see if the t cell or be cell receptors to see if the populations are clonal -> neoplastic
or
polyclonal -> multiple different cell types -> inflammatory
you would not want to give chemo to a dog with inflammatory issues.
What is indicated with the orange lines? The green lines?
What is seen in this image? What does each colored arrow represent?
What is important to remember when considering a leukemia diagnosis?
What is this teal arrow pointing to?
Megakaryocyte
Where is erythropoietin produced? What disease process can affect it and why?
- Epo is produced in the kidney (especially in the peritubular interstitial cells) and liver.
- Ckd - effects the cells -> thus decrease of epo production.
What can be seen in a blood smear, in regards to the red blood cells, that can indicate pathology is occuring?
Presence of polychromatophils and metarubricyte in blood smears usually indicate some kind of pathology is going on, this is not normal.
What cell does neutrophil, eosinophils, and basophils all derive from? monocytes?
Myeloblasts
monoblasts
What types of lymphoma are of high suspicion for a cat with FELV?
Cats that have FELV you typically see mediastinal and multi-centric T cell lymphoma and its in young cats.