Test 4: 6: bone marrow Flashcards
what are the primary lymphoid organs
thymus
bone marrow
bursa of fabricius
(make B and T cells)
secondary lymphoid organs
▪ Spleen ▪ Lymph nodes ▪ MALT ▪ Tonsils
how do T cells form
start in bone marrow, move to thymus (cortex to medulla), mature and selected into naive CD4 or CD8, go out into the periphery
T cells move into paracortical regions of LN and periarteriolar sheaths of spleen.
will mature into helper(CD4) or cytotoxic(CD8) T cells when presented with antien peptide attached to MHC
how do B cells form
start in bone marrow, move to follicle in secondary lymphoid organ, mature into plasma cells that make antibodies
- Ag-independent phase in primary lymphoid tissues (BM, ileal Peyer’s patches). Following this phase, B cells express IgM and IgD on surface that signifies a mature B cell.
- Ag-dependent phase in secondary lymphoid tissues (spleen, LN, tonsils, Peyer’s patches). In this phase, Ag-activated mature B cells differentiate into IgM-secreting plasma cells or switch to another antibody isotype.
B cells live in follicles of lymphnodes, spleen or GALT/MALT and can see soluable Ag
what causes atrophy of the lymphoid system
Immunodeficiency disorders
Viruses: Infectious agents: e.g. CDV, EHV-1, Feline panleukopenia virus, FIV, BVDV, Hog Cholera virus
Toxins: e.g. halogenated aromatic hydrocarbons, fumonisins, aflatoxin
Chemotherapeutic agents & Ionizing radiation: e.g. azathioprine, cyclosporine, corticosteroids
Malnutrition: mediated by the hormone leptin
Cachexia
Aging
what are two common neoplasma
Thyoma
Lymphoma
Thymoma grows — and is assocaited with — disease
slowly, rarely metastazise
Myasthenia gravis (Auto-antibodies to Ach receptors and blocks function)
exfoliative dermatitis- seen most often cats, also reported dog and ra
Myasthenia gravis is caused by autoantibodies to ACh receptor and is exacerbated by exercise, — and may lead to —
megaesophagus
aspiration pneumonia
common to have thymoma that causes this
Thymoma are derived from the — component with variable benign lymphocytic infiltration
epithelial
Lymphoma in cats is often associated with —
FELV +
young cats
what are some things that cause small/absent lymph nodes
- Developmental disorders (hypoplasia): primary immunodeficiency disease
- Lack of antigenic stimulation: SPF(lab) animals
- Malnutrition
- Age
- Viral Infections (CDV, BVD, etc.)
- Radiation
regional or generalized enlargement of lymphnode with unknown or unspecified cause
Lymphadenopathy
explain why reactive hyperplasia causes large lymph node
lymph node doing its job to fight infection
antigen enters lymphnode, interacts with T cell, T cell moves into follicle and triggers selection of B cells which eventually mature into plasma cells that release antibody into the blood
will see alot of cell types = normal function
enlarged lymph node shows
lymphoid hyperplasia
many cell types, lymph node doing its job making antibody to antigen
what caused the enlarged lymphnode
drainage, could be secondary to surgery
will cause enlarged lymph node, but not dangerous
can see widened subcapsular sinus filled with edema and lots of RBC
what causes lymphandenitis
lymph node tissue replaced by inflammatory cells (neutrophils ect)
acute: soft, red, edema
chronic: capsule, firm, painful
can be caused by bacteria, virus, fungu, protozoa
enlarged lymph node caused by
FIP lymphadenitis
enlarged lymphnode that ruptured is caused by what bacteria?
strangles
strep equi ssp equi
what causes casseous lymphadenitis
C. pseudotuberculosis
what kind of cancer spreads to lymphnodes
carcinomas (epithelial origin)
what kind of cancer, effects Bernese Mtn Dogs, Rotties and golden retrievers
histiocytic sarcoma
round cell tumor
interstitial dendritic cell origin
lymphoma, plasma cell, mast cell, histiocytic, TVT
localized Histiocytic Sarcoma are found
spleen, lymph node, lung, bone marrow, skin and subcutis especially of extremities
lymphoma, plasma cell, mast cell, histiocytic, TVT
disseminated histiocytic sarcoma is found
secondary sites are widespread, but consistently include liver and lung (with splenic primary), and hilar lymph node (with lung primary), other visceral sites and bone marrow
lymphoma, plasma cell, mast cell, histiocytic, TVT
what are some things that cause pigment in a lymph node
drainage of areas with hemosiderin (red blood cell breakdown)
melanin
tattoo
parasites
red pulp of the spleen does what
filters blood of foreign material, microorganisms and antigens
stores mature erythrocytes
preforms hematopoiesis
what does white pulp of spleen do?
T cells surround arterioles (periarteriolar lymphoid sheaths/PALS) will capture antigen and bring them to B cells inside lymphoid follicles
will mature into plasma cells that make antibodies or memory B cells
if you have big spleen that oozes blood when cut what three things:
Congestion
* Torsion: occurs in pigs and dogs (+/- GDV)
* Barbiturate euthanasia, anesthesia (dogs, horses)
Septicemia
→microbes transported to spleen→rapidly phagocytized by macrophages (e.g. Bacillus
anthracis). leads to hyperemia (increased blood flow)
Acute Hemolytic Anemias:
tries to remove broken RBC from circulation
big bloody spleen caused by
Congestion: torsion or barbiturate
septicemia
acute hemolytic anemia
what are some causes of large spleen with firm/meaty texture
chronic infection
chronic hemolytic anemia
diffuse granulomatous diease (mycobacterius, TB, Brucella)
Follicular lymphoid hyperplasia
Cancers: lympoma, mast cell, myeloma
storage diseases
extramedullary hematopoiesis: trigger signals to make new cells
enlarged spleen, meaty
lymphoma- cause pink color
type of round cell tumor: lymphoma, plasma, TVT, histiocytic, mast cell
other cancers: Lymphoma, mast cell tumor/mastocytosis, multiple myeloma, lymphoproliferative diseases
cat large spleen caused by
mast cell tumor
type of round cell tumor: lymphoma, mast, plasma, TVT, histiocytic
spleen of feret
Extramedullary hematopoiesis (EMH): hormonal or physiologic mechanisms signal synthesis of progenitor cells for systemic circulation; however, splenic EMH often incidental.
4 causes of nodular spleen with bloody consistency
- Hematomas (induced by nodular hyperplasia or trauma)
- Hemangiosarcoma
- Incomplete/irregular contraction of smooth muscle trabeculae that cause areas that look like pooled blood
- Acute splenic infarcts
what can cause this, bloody inside
- Hematomas (induced by nodular hyperplasia or trauma)
- Hemangiosarcoma
- Incomplete/irregular contraction
- Acute splenic infarcts
- Hematomas (induced by nodular hyperplasia or trauma)
- Hemangiosarcoma
- Incomplete/irregular contraction
- Acute splenic infarcts
spleen
- Hematomas (induced by nodular hyperplasia or trauma)
- Hemangiosarcoma
- Incomplete/irregular contraction
- Acute splenic infarcts
nodular spleen with firm consistency can be what 4 things
- Nodular hyperplasia
Simple – lymphoid follicles Complex (previous known as fibrohistiocytic nodules) – lymphoid follicles + fibrohistiocytic proliferation - Granulomas (Mycobacterium)
- Abscesses (Strep, Rhodococcus, Arcanobacterium, Corynebacterium)
- Neoplasms
* Primary: lymphoma (including nodular indolent lymphomas), histiocytic sarcoma, leiomyosarcoma,
fibrosarcoma, undifferentiated sarcomas.
* Metastatic: many sarcomas and carcinoma
nodular hyperplasia that causes splenic nodules with firm consistency can be simple — or complex—
Simple – lymphoid follicles
Complex (previous known as fibrohistiocytic nodules) – lymphoid follicles + fibrohistiocytic proliferation
primary neoplasma that cause splenic nodules with a firm consistency are
lymphoma (including nodular indolent lymphomas)
histiocytic sarcoma
leiomyosarcoma
fibrosarcoma
undifferentiated sarcomas.
metastic neoplasms that cause splenic nodules with a firm consistency are
many sarcomas and carcinomas
what can cause abscesses in the spleen that present as splenic nodules with a firm conistency
Strep, Rhodococcus, Arcanobacterium, Corynebacterium
spleen nodular but firm
1.focal nodular hyperplasia: simple or complex
2.granuloma/abscess
3.neoplasia
nodular spleen with firm consistency
1.focal nodular hyperplasia: simple or complex
2.granuloma/abscess
3.neoplasia histiocytic
round cell: TVT, histio, lymphoma, mast, plasma
1.focal nodular hyperplasia: simple or complex
2.granuloma/abscess
3.neoplasia
splenic stromal sarcomas
3 causes of small spleens
- Developmental: immunodeficiency diseases
- Atrophy: aging or wasting diseases
- Contraction
baby spleen
Splenic Choristoma:
Developmental: normal tissue at an abnormal site. “Daughter or progeny spleens”
Acquired: traumatic rupture, “Splenosis”
baby spleens made by trauma or rupture are called —
splenosis
choristoma (normal tissue in weird place)
Siderofibrotic Plaques:
Grey-tan plaques on capsule with accumulation of iron/hematoiden and calcium
Common incidental finding in aged dogs
why no metastatic tumors in the tonsil
Tonsils do not have afferent lymphatics and do not filter lymph.
Therefore, only primary or
hematogenous infections occur.
Tonsils do not have — lymphatics and do not filter lymph. Therefore, only primary or hematogenous infections occur.
afferent
small tonsils can be caused by
viral infections that cause immunosuppression
rare
what kind of neoplasia in a tonsil
Squamous cell carcinoma
Lymphoma
Melanoma
only primary tumors- NO afferent lymphatics
poly of tonsil
benign
what kind of cancer if firm, unilateral and lobulated
SCC
firm because of desmoplasia
Tonsils can have only primary tumors: Squamous cell carcinoma, lymphoma, malignant melanoma
soft, bulging, bilateral cancer of tonsils
lymphoma
tonsils can only get primary tumors: Squamous cell carcinoma, lymphoma, malignant melanoma
what happens to arabian foal with SCID
Severe Combined Immunodeficiency
Autosomal recessive trait expressed as an absence of functional B & T lymphocytes
Defect in DNA-dependent protein kinase, an enzyme required for receptor gene rearrangements involved in maturation of B & T cells
Prone to infection and dies within 5 months
will have small thymus, spleen and lymph nodes
animals with — will have short life span and a small thymus, spleen and lymph nodes
Severe Combined Immunodeficiency (SCID)
arabian foals, bassett hounds, jack russels, cardigan welsh corgis
small cell lymphoma vs large cell lymphoma
small: nucleus same size as RBC
large: nucleus 2x the size of RBC
how to figure out type of lymphoma
Nodular or diffuse
Cell Size (small, intermediate, large)
Mitoses/grade (indolent, low, mid, high) Immunophenotype (B or T)
explain immunohistochemisty and how to it used to diagnosis lymphoma
if cell has antigen it will turn brown
used to determine phenotype of cells in a sample (B cell, T cell, NK ect)
canine LSA is most commonly —
diffuse large B cell lymphoma (DLBCL) or peripheral T cell Lymphoma (PTCL)
will have LN enlargment that is soft, tan and bulging
happens in middle aged dogs- no viral causes found yet
— is associated with peripheral T cell lymphoma in dogs
hypercalcemia (15%)
— is a T cell marker
CD3
— are B cell markers
CD79a
Pax-5
T zone lymphoma is common in dogs and is a — subtype
indolent- slow growing can last for years without treatment
usually starts in mandibular lymph node
why type of lymphoma
T zone lymphoma
last for years- indolent
— is nodular, small cell, indolent, T cell in dogs
T zone lymphoma
— is diffuse, large cell, high grade, B cell in dogs
Diffuse large B cell lymphoma
— causes a 60x increase risk of lymphoma in cats
FeLV
FeLV infects T cells and leads to — syndrome which can lead to — and —
Myelodysplastic syndrome
acute myeloid leukemias
T cell LSA/leukemia
thymic lymphoma in cats can spread —
Thymus, mediastinum, sternal LNs or multicentric
seen in FeLV cats
— is the most common lymphoma in cats
Type 2 small cell enteropathy-associated T cell lymphoma (EATL)
GI lymphoma
May arise within inflammation (IBD) and thus require PCR for antigen receptor
rearrangement testing for clonality (PARR).
what test to diagnose EATCL
PARR
PCR for antigen receptor rearrangement
tests the clonality of the T cell receptor or the immunoglobulin receptor (B cell)
a genotyping study
spike= cancer
curve= inflammation
what are some GI lymphomas in cats that are full thickness and nodule and can cause obstruction
Diffuse Large B cell lymphoma
Large granular lymphocyte lymphoma (most cytotoxic T cell, some NK cells)
two forms of lymphoma that infect cows
BLV-associated lymphoma (Enzootic bovine leukosis):
Non-BLV lymphoma (sporadic form): most often T cell LSA
Non-BLV lymphoma (sporadic form): most often T cell LSA has three forms
Calf/juvenile form: fetuses and calves (6mos)
Thymic form: beef cattle 6-24mos
Cutaneous form: young cattle 1-3yrs
Lymphoma in cows
BLV associated lymphoma is also called
Enzootic bovine leukosis
BLV-associated lymphoma causes
Polyclonal B lymphocyte lymphocytosis
that can develop into leukemia/lymphoma
infects:Superficial/abdominal LN, retrobulbar, abomasum, heart, uterus, spleen, kidney.
survival: 6-8 years
Non-BLV lymphoma is most often — cells
T cell
BLV invades and integrates into the genome of infected B cells, resulting in a — lymphocytosis in about 30% of cattle. In approximately 1-5% of BLV-infected cattle, a single clone will emerge, leading to the development of B cell —
polyclonal B lymphocyte
leukemia/lymphoma.
— is the most common lymphoma in horses
T cell rich B cell lymphoma
thymomas in dogs are associated with what condition
Myasthenia gravis
common sequela of Myasthenia gravis
aspiration pneumoma
assiciated with thymomas in dogs
FeLV assiciated lymphoma in cats in seen primarly in what location
mediastinal and multicentric
spleen from a 14 year old lab. Diagnosis?
no blood ooze
Lymphoma, mast cell tumor/mastocytosis, multiple myeloma, lymphoproliferative diseases
chronic disease
follicular lymphoid hyperplasia
neoplasia
storage disease
extramedullary hematopoiesis
spleen
diagnosis
- Hematomas (induced by nodular hyperplasia or trauma)
- Hemangiosarcoma
- Incomplete/irregular contraction
- Acute splenic infarcts
which of the following does not cause enlarged lymph nodes
metastatic mammary carcinoma
X-SCID
lymphoma
mycobacterium bovis
X-SCID
basset-hound
small/no lymphoi organs
death in months
which of the following is not a common cause of aquired immunodeficency
parvo
corticosteroids
malnutrition
DNA-PKs mutation
canine distemper
DNA-PKs mutation
what are some causes of acquired immunodeficiencies
- Pregnancy
- Aging
- Malnutrition
- Toxins (poly-chlorinated -brominated biphenyls, iodine, lead, cadmium, methylmercury, DDT)
- Drugs (corticosteroids, chemotherapeutic agents (cyclosporin A, cyclophosphamide…)
- Viral infections
Peripheral blood reticulocytosis accompanies — , i.e., anemias resulting in marrow erythroid hyperplasia.
regenerative anemias
Anemias secondary to erythroid hypoplasia are —
non-regenerative.
what type of anemia has reticulocytes present?
regenerative
secondary to erythroid hyperplasia
What are potential causes for an increase in the M:E?
myeloid hyperplasia
erythroid hypoplasia
What are potential causes for a decrease in the M:E?
decrease in M:E
decrease in M- hypoplasia- anemia, iron deficiency, malnutiriton
increase in E: hyperplasia- regenerative anemia
How might you distinguish a decrease in the M:E secondary to erythroid hyperplasia from a decrease secondary to myeloid hypoplasia?
erythroid hyperplasia- regenerative anemia- high polychromasia and reticulocyte
myeloid hypoplasia- leukopenia
use CBC
Conversely how can you distinguish an increase in the M:E secondary to myeloid hyperplasia from an increase due to erythroid hypoplasia?
CBC
myeloid hyperplaia- high white count
erythroid hypoplasia- non-regenerative anemia
Estimate the M:E for IMHA. Will it be high, low, normal?
low becuase E increases trying to make new RBC secondary to the IMHA
What is your interpretation of the bone marrow response with regard to the CBC data for this patient (i.e. hematocrit)?
immune-mediated hemolytic anemia (IMHA).
Hematocrit = 13% (ref interval 37-55%)
Cytologic Findings: Spherocytosis and polychromasia are noted on the peripheral bloodsmear.
Erythroid hyperplasia
What are some associated clinical signs you may see in your patient with IMHA
Signs of anemia such as pallor and weakness. If the patient has thrombocytopenia, you may also see petechiae of the mucosa and skin, and possible melena.
What is the most likely diagnosis for this patient?
DOG
squamous cell carcinoma
dog
What is the most likely diagnosis for this patient?
lymphoma
cat
Based on the gross and histopathologic lesions, what is the most likely diagnosis?
thymic lymphoma
cats with thymic lymphoma are — and usually have —
young
FeLV
dog
Male beagle with a history of difficulty breathing and exercise intolerance.
What is the most likely diagnosis for this dog?
thyoma
dogs with thyoma usually are —
old
What are the possible sequelae of thyomas in this dog?
Myasthenia gravis, which can lead to megaesophagus and aspiration pneumonia.
cat
What are some possible causes of this lesion?
Causes of necrotizing lymphadenitis include a variety of bacterial, viral, protozoal and fungal organisms. This case shows numerous intralesional fungal organisms.
descrpition and morpholigical diagnosis
The nodal architecture is effaced by regions of necrosis and an extensive inflammatory cell infiltrate (neutrophils, epithelioid macrophages, giant cells). Within the lesion are numerous large round organisms.
Severe necrotizing lymphadenitis with intralesional fungal organisms (morphology consistent with Coccidioides immitis).
dog spleen
In general, what are some possible causes of this lesion in domestic animals?
There are many possible causes for diffuse splenomegaly with a meaty consistency. The most common in older dogs and cats is neoplasia (lymphoma, mast cell tumor, multiple myeloma, lymphoproliferative disease).
diffuse splenomegaly with meaty conisistency: chronic disease, follicular lymphoid hyperplasia, cancer, storage disease, extramedullary hematopoiesis
Based on the gross and histopathologic lesions, what is the cause of the splenomegaly in the dog?
large pink spleen
lymphoma
ferret spleen
Based on the photomicrographs below, what is the cause of the splenomegaly in the ferret?
extramedullary hematopoiesis
Based on the photomicrographs below, what is the cause of the splenomegaly in the cat?
mast cell tumor/mastocytosis
Which of the species does not have a definitively confirmed viral cause of lymphoma?
dog
Which of the following patients likely does NOT have increased M:E on bone marrow evaluation?
5-year-old Jack Russell terrier with severe immune mediate hemolytic anemia and thrombocytopenia
14-year-old domestic short hair cat with chronic renal failure
4-year-old female Rottweiler with pyometra
8-year-old Labrador retriever with hypothyroidism
3-year-old mixed breed dog with multiple subcutaneous abscesses
5-year-old Jack Russell terrier with severe immune mediate hemolytic anemia and thrombocytopenia
To aid in a diagnosis, what concurrent test would need to be submitted?
bone marrow evaluation?
5-year-old Jack Russell terrier with severe immune mediate hemolytic anemia and thrombocytopenia
CBC
A 4-month-old Arabian foal is euthanized. The necropsy reveals severe diffuse pneumonia and markedly hypoplastic thymus, spleen and lymph nodes. What is the most likely diagnosis?
Correct answer:
SCID, autosomal recessive
Chediak-Higashi Syndrome
SCID, X-linked (X-SCID)
Leukocyte Adhesion Deficiency
SCID, autosomal recessive
Which of the following is/are NOT counted as myeloid in the M:E ratio determination (mark all that apply)?
Correct answer:
megakaryocyte
metarubricyte
myelocyte
band cell
basophil
megakaryocyte
metarubricyte
All of the following are appropriate indications for performing a bone marrow aspirate EXCEPT?
Correct answer:
Patient with regenerative anemia and leukocytosis with normal platelet count
Patient with lymphoma
Patient with atypical immature cells in circulation
Patient with persistent nonregenerative anemia
Patient with Fever of unknown origin
Patient with regenerative anemia and leukocytosis with normal platelet count
