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Shannon Martinson, March 2011 Pathology of the Hematopoietic System Lecture 3: Spleen and thymus

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Page 1: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Shannon Martinson, March 2011

Pathology of the Hematopoietic

System

Lecture 3: Spleen and thymus

Page 2: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Spleen – Structure and Function

• 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

Normal spleen from a cat 1 cm

Page 3: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Structure Function

Red Pulp • Sinusoids/vascular spaces

• Splenic cords

• Filters blood -removal of foreign material(phagocytosis)

• RBC storage• Hematopoiesis

(EMH)

White Pulp • Periarteriallymphatic sheaths (PALS) (T-cells)

• Lymphoid nodules (B-cells)

• Marginal zone (Macrophages)

• Immuneresponse

Spleen – Structure and Function

Page 4: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Miscellaneous Diseases

Circulatory diseases of the spleen

Inflammation of the spleen (splenitis)

Adaptations of growth

- Aplasia/Hypoplasia, Hyperplasia, Atrophy

Primary and secondary splenic neoplasia

Diseases of the spleen

Page 5: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Spleen – Miscellaneous diseases

Misc. Diseases

Splenic lymphoid necrosis

Siderofibrosis (Gamna-gandy bodies)

Hemosiderin deposition/ hemosiderosis

Splenic amyloidosis

Splenic contraction

Page 6: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Misc. Diseases

Splenic lymphoid necrosis

Siderofibrosis (Gamna-gandy bodies)

Hemosiderin deposition/ hemosiderosis

Splenic amyloidosis

Splenic contraction

Splenic lymphoid necrosis

Viral infections

• Panleukopenia virus

• Canine parvovirus

• Bovine viral diarrhea virus

• Equine viral rhinotracheitis

Toxins

Aging

Spleen – Miscellaneous diseases

Splenic lymphoid necrosis in a puppy with canine herpesvirus

Page 7: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Gross: Granular white-

yellow deposits in the

splenic capsule

Siderofibrosis = Gamna-Gandy bodies

• Incidental finding/senile change• Possible sequela of prior hemorrhage

Spleen – Miscellaneous diseases

Page 8: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Siderofibrosis = Gamna-Gandy bodies

• Incidental finding/senile change• Possible sequela of prior hemorrhage

Histo: Hematoidin,

hemosiderin and

mineral deposits

Dr MD McGavin, College of Veterinary Medicine, University of Tennessee

Spleen – Miscellaneous diseases

Gross: Granular white-

yellow deposits in the

splenic capsule

Page 9: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic amyloidosis

• Usually 2 amyloidosis -

chronic inflammation

• Gross: Splenomegaly, beige

to orange discolouration

• Histology: Deposition of

amyloid around the follicular

arteries (Congo red stain)

Hemosiderin deposition/Hemosiderosis

• A small amount of hemosiderin within macrophages in the spleen is

normal → normal rbc turnover

• Increases with increased erythrocyte destruction (IMHA for eg)

College of Veterinary Medicine, University of Illinois

Spleen – Miscellaneous diseases

Page 10: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic contraction

• Contraction of the smooth muscle in the capsule/trabeculae

• Occurs with catecholamine release, shock, acute splenic rupture

• Gross: Small dry spleen with wrinkling of the capsule

Spleen – Miscellaneous diseases

Page 11: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic contraction

• Contraction of the smooth muscle in the capsule/trabeculae

• Occurs with catecholamine release, shock, acute splenic rupture

• Gross: Small dry spleen with wrinkling of the capsule

Contraction can be incomplete:

Grossly, looks very similar to

splenic infarction

Spleen – Miscellaneous diseases

Page 12: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic contraction

• Contraction of the smooth muscle in the capsule/trabeculae

• Occurs with catecholamine release, shock, acute splenic rupture

• Gross: Small dry spleen with wrinkling of the capsule

Compare to splenic infarction

Contraction can be incomplete:

Grossly, looks very similar to

splenic infarction

Spleen – Miscellaneous diseases

Page 13: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic rupture

• Fairly common

• Primary - trauma

• Secondary to splenomegaly, splenic neoplasia

• Potential sequelae include hemoabdomen and

splenosis

Splenic rupture 2 to

hemangiosarcoma in a dog

Splenic rupture and hemoabdomen 2

to splenomegaly (lymphoma) in a pig

Spleen – Miscellaneous diseases

Page 14: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic rupture - splenosis

• Seeding of splenic explants on

peritoneal surfaces forming

accessory spleens

Gross: Small red nodules

within the omentum

Histology: Looks like

normal spleen

Can be mistaken for hemangiosarcomametastases

Image: Cornell Veterinary Medicine

Spleen – Miscellaneous diseases

Page 15: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Circulatory disturbancesActive hyperemia

Passive congestion

Splenic infarction

Splenic hematoma

Splenic torsion

Spleen – Circulatory disturbances

Page 16: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Congested vs normal spleen

Passive congestion

• Vascular pooling (shock)

• Barbiturate

administration**

• Hemolytic anemia

Similar grossly:

• Splenomegaly

• Red to purple

• Oozes blood on cut surface

Active hyperemia

• Acute systemic infection

Spleen – Circulatory disturbances

Page 17: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Passive congestion

• Vascular pooling (shock)

• Barbiturate

administration**

• Hemolytic anemia

Active hyperemia

• Acute systemic infection

College of Veterinary Medicine, University of Illinois

Spleen – Circulatory disturbances

Similar grossly:

• Splenomegaly

• Red to purple

• Oozes blood on cut surface

Page 18: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic congestion from barbiturate

euthanasia in a horse – marked

splenomegaly

Dr MD McGavin, College of Veterinary Medicine, Univerity of Tennessee

Histology: Red pulp dilated

and contains blood; the white

pulp is widely separatedDr MD McGavin, College of Veterinary Medicine, Univerity of Tennessee

Spleen – Circulatory disturbances

Page 19: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic infarction is caused by:

a) Vascular damage

b) Hypercoagulable states

c) Splenomegaly (of any cause)

d) Septic emboli– Showering from endocarditis (mitral or aortic)

Splenic infarcts

Dr MD McGavin, College of Veterinary Medicine, Univeristy of Tennessee

Gross Lesions:Acutely: infarcts are

discrete, raised, and

dark red – at the

margins of the organ

With time: pale and firm

(fibrosis)

Spleen – Circulatory disturbances

} Due to thrombosis

Page 20: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Gross: Red nodular mass.

Splenic hematoma

• Common in dogs

• Trauma*

• Often associated with nodular

hyperplasia or vascular tumours

College of Veterinary Medicine, University of Illinois

Spleen – Circulatory disturbances

Need histology to

rule out underlying

neoplasia!

Page 21: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic torsion

• Dogs and pigs

• With or without the stomach

• Twists around the gastrosplenic ligament

Gross: Splenomegaly, blue to

black, folded back on itself

Spleen – Circulatory disturbances

Page 22: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Spleen – Inflammation

• Tularemia (Francisella tularensis)

• Yersiniosis (Yersinia pseudotuberculosis)

Gross: Multifocal miliary white foci within the spleen. • Can see similar lesions in the lymph nodes and liver

• Older lesions resemble granulomas/abscesses

Acute splenitis – Multifocal necrosuppurative splenitis

Tularemia in a beaver

Page 23: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Spleen – Inflammation

From: Recognizing African Swine Fever:: A field manual FAO Animal Health Manual

African swine fever

Acute splenitis – Septicemic splenitis

• Hog cholera

• African swine fever

• Anthrax**Gross Findings• Splenomegaly• Dark discolouration• Engorged with viscous blood

Page 24: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Acute splenitis – Septicemic splenitis

• Thrash metal band from the 80’s?

• Disease caused by: Bacillus anthracis

• Zoonotic

• In ruminants – septicemic disease

• In horses, pigs and dogs – pharyngeal and enteric disease

Spleen – Inflammation

Page 25: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Anthrax – Pathogenesis in ruminants:

Ingestion / wound contamination / inhalation

Lymphangitis and localized lymphadenitis

Massive bacteremia (sepsis) and toxemia

Increased vascular permeability and impaired coagulation

Sudden Death

• With sepsis, huge numbers of vegetative organisms in blood

• Become spores when exposed to air

• Very resistant

• Survive decades in soil

• Infections often occur following soil excavation

sherwords.blogspot.com

Spleen – Inflammation

Page 26: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Anthrax - Lesions in ruminants

• Take a blood smear from the ear!

• Methylene blue stain: Short chains of large bacilli with distinct pink capsule and square ends

http://flickr.com/photos/33944290@N05/3164658908

Characteristic Findings:

• Bloated autolysed carcass with blood oozing from the orifices

• You aren’t supposed to necropsy suspect cases!!

Department of Pathobiology, University of Guelph

Spleen – Inflammation

Page 27: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

• Marked splenomegaly: Dark red to black, soft to semi-fluid spleen

• Multifocal hemorrhage and edema in connective tissue

• Thick tarry blood: fails to clot

Cornell Veterinary Medicine

Potential for bioterrorism?

Spleen – Inflammation

Anthrax - Lesions in ruminants

Page 28: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

• Diffuse

granulomatous

splenitis:

• Histoplasmosis

• Blastomycosis

• Nodular

granulomatous

splenitis:

• Avian

mycobacteriosis

• Bovine

tuberculosis

Chronic splenitis: Granulomatous splenitis

Mycobacterium avium infection in a turkey

Dept of Veterinary Biosciences, The Ohio State University

Histoplasmosis in a dog

Spleen – Inflammation

Page 29: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Growth disturbances

Aplasia

Atrophy

Benign nodular hyperplasia

Lymphoid hyperplasia

Hyperplasia of the monocyte-macrophage system

Extramedullary hematopoiesis

Spleen – Disturbances of growth

Page 30: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Importance: Rule-out neoplasia

Benign nodular hyperplasia

• Common finding in old dogs

• Usually incidental

• May predispose to splenic hematomas

Images: Dr MD McGavin, College of Veterinary Medicine, Univerisity of Tennessee

Gross: Gray to red

nodular mass(es):

composed of lymphoid

tissue and red pulp

Spleen – Disturbances of growth

Page 31: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Lymphoid hyperplasia

• Hyperplasia of the white pulp

• Response to blood-borne antigen/chronic antigenic

stimulation

Lymphoid follicles visible as 1 – 3 mm foci

Spleen – Disturbances of growth

Page 32: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Histiocytic sarcoma, dog

* Covered in primary hematopoietic neoplasia

Primary splenic neoplasiaLymphoproliferative diseases:Lymphoma/Leukemia*

Myeloproliferative diseases: Histiocytic sarcoma*Mastocytosis*

Hemangioma

Hemangiosarcoma

Others: Fibrosarcoma, Fibrohistiocytic nodules, etc

Leukemia/Lymphoma, dog

Lymphoma, cat

Mastocytosis, cat

Spleen – Primary neoplasia

Page 33: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Gross: Single, soft, dark

red nodular mass

Cornell Veterinary Medicine

Histology: Cavernous

blood-filled spaces lined

by a well-differentiated

endothelium

Splenic hemangioma

• Benign mass of endothelial origin

Spleen – Primary neoplasia

Page 34: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic hemangiosarcoma

• Most common malignant tumour of the

canine spleen

Gross:

• Single to multiple, discrete to

coalescing dark red masses

• +/- metastases

Spleen – Primary neoplasia

Page 35: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic hemangiosarcoma

• Most common malignant tumour of the

canine spleen

Spleen – Primary neoplasia

Gross:

• Single to multiple, discrete to

coalescing dark red masses

• +/- metastases

Page 36: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Splenic HemangiosarcomaHistology:

• Blood-filled vascular

spaces lined by

anaplastic endothelial

cells

Possible sequelae: Splenic rupture, hemoabdomen , peritoneal seeding, metastasis

Spleen – Primary neoplasia

Page 37: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Metastatic splenic tumours: dog with pancreatic carcinoma

Spleen – Secondary (metastatic) neoplasia

Page 38: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

• White to tan, lobulated organ within the anterior mediastinum

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

Thymus – Structure and function

Page 39: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

• Structure

– Composed of epithelial tissue and lymphoid tissue

– Split into cortical and medullary areas

• Function

– Proliferation & maturation of T cells

Thymus – Structure and function

Page 40: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Thymus – Miscellaneous diseases

Miscellaneous diseases

Lymphocytolysis/thymic atrophy

Thymic aplasia/hypoplasia

Thymic hemorrhage/hematoma

Can lead to acquired immunodeficiency

Congenital immunodeficiency

Page 41: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Miscellaneous diseases

Lymphocytolysis/thymic atrophy

Thymic aplasia/hypoplasia

Thymic hemorrhage/hematoma

Thymic hemorrhage:

• In dogs, sudden death is sometimes seen

due to hypovolemic shock resulting from

massive thymic/mediastinal hemorrhage

• Several implicated causes: trauma, ruptured

aorta, anticoagulant rodenticide

Cornell Veterinary Medicine

Thymus – Miscellaneous diseases

Page 42: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Thymic Lymphoma

Neoplastic proliferation of

T-lymphocytes

Often younger animals (cats, calves, and dogs)

Thymoma

Neoplastic proliferation of thymic epithelial cells

Slow growing, encapsulated, rarely metastasize

Myasthenia gravis (dogs)

Cornell Veterinary MedicineDr MD McGavin, College of Veterinary Medicine, University of Tennessee

Thymus – Primary neoplasia

Page 43: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Thymus – Primary neoplasia

Thymic lymphoma in a dog

Page 44: Pathology of the Hematopoietic System - people.upei.capeople.upei.ca/smartinson/Hemat-L3-11_Shannon.pdf · Pathology of the Hematopoietic System ... Histology: Looks like normal spleen

Questions?