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Shannon Martinson, March 2013 Pathology of the Hematopoietic System Lecture 3: LN (continued), Thymus and Spleen

Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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Page 1: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Shannon Martinson, March 2013

Pathology of the Hematopoietic

System

Lecture 3: LN (continued), Thymus

and Spleen

Page 2: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Primary lymph node neoplasia = Lymphoma

Lymph node: Neoplasia

Covered in primary hematopoietic neoplasia*

Page 3: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

• Lymph node metastasis:

• Common with carcinomas, melanomas, mast cell tumors…

• May see lymph node enlargement

• Variable effacement of normal architecture

•One basis of staging tumor malignancy

• Stage 0: regional node normal

• Stage 1: regional node enlarged but still freely moveable

• Stage 2: regional node enlarged and fixed

Lymph node: Neoplasia

Secondary lymph node neoplasia

Page 4: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Metastasis of mammary

carcinoma to a lymph node

Lymph node: Secondary neoplasia

Images: Courtesy of Dr Hanna, AVC

Page 5: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

• White to pink, 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 6: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

• Structure

– Composed of epithelial tissue and lymphoid tissue

– Lobulated and split into cortical and medullary areas

• Function

– Proliferation & maturation of T cells

Thymus – Structure and function

Normal thymus

Page 7: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Thymus – Miscellaneous diseases

Miscellaneous diseases

Lymphocytolysis/thymic atrophy

Thymic aplasia/hypoplasia

Thymic hemorrhage/hematoma

Can lead to acquired immunodeficiency

Congenital immunodeficiency

Cornell Veterinary Medicine

Page 8: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Thymus – Primary neoplasia

General Features: • Space occupying mass in

cranial mediastinum • Dyspnea • 2 main differentials

Page 9: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Thymic Lymphoma

Neoplastic proliferation of

T-lymphocytes

Often younger animals (cats, calves, and dogs)

Malignant behaviour

Thymus – Primary neoplasia

Thymoma

Neoplastic proliferation of

Epithelial cells

Less common – dogs, sheep goats

Slow growing, encapsulated

Page 10: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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 11: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Structure Function

Red Pulp • Sinusoids/vascular spaces

• Splenic cords

• Filters blood - removal of foreign material (phagocytosis)

• RBC storage • Hematopoiesis

(EMH)

White Pulp

• Periarterial lymphatic sheaths (PALS) (T-cells)

• Lymphoid nodules (B-cells)

• Marginal zone (Macrophages)

• Immune response

Spleen – Structure and Function

Page 12: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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 13: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Spleen – Miscellaneous diseases

Misc. Diseases

Siderofibrosis (Gamna- gandy bodies)

Splenic Amyloidosis

Splenic Contraction

Splenic Rupture

Splenic Torsion

Page 14: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Gross: Granular white-yellow deposits in the splenic capsule

Spleen – Miscellaneous diseases

Normal spleen

Siderofibrosis = Gamna-Gandy bodies

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

Page 15: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Histo: Hematoidin, hemosiderin and mineral deposits

Siderofibrosis = Gamna-Gandy bodies

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

Spleen – Miscellaneous diseases

Page 16: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Splenic amyloidosis

• Usually 2° amyloidosis - chronic inflammation

• Gross: Splenomegaly, beige to orange discolouration

College of Veterinary Medicine, University of Illinois

Normal spleen

Spleen – Miscellaneous diseases

Page 17: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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

Normal spleen

Spleen – Miscellaneous diseases

Page 18: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Contraction can be incomplete: Grossly, looks very similar to splenic infarction

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 19: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Compare to splenic infarction

Contraction can be incomplete: Grossly, looks very similar to splenic infarction

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 20: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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 21: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Splenic rupture → splenosis

• Seeding of splenic explants on peritoneal surfaces forming accessory spleens

Gross: Small red nodules within the omentum

Can be mistaken for hemangiosarcoma metastases

Image: Cornell Veterinary Medicine

Spleen – Miscellaneous diseases

Page 22: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Gross: Small red nodules within the omentum

Histology: Look like small (normal) spleens

Image: Cornell Veterinary Medicine

Splenic rupture → splenosis

• Seeding of splenic explants on peritoneal surfaces forming accessory spleens

Spleen – Miscellaneous diseases

Page 23: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Splenic torsion

• Dogs and pigs • With or without the stomach (GDV*) • Twists around the gastrosplenic ligament

Gross: Splenomegaly,

blue to black,

folded back on

itself

Spleen – Miscellaneous diseases

Page 24: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Circulatory disturbances

Active hyperemia

Passive congestion

Splenic infarction

Splenic hematoma

Spleen – Circulatory disturbances

Page 25: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Congested vs normal spleen

Active hyperemia

• Acute systemic infection

Passive congestion

• Vascular pooling (shock) • Barbiturate administration** • Hemolytic anemia

Similar grossly: • Splenomegaly • Red to purple • Oozes blood on cut surface

Spleen – Circulatory disturbances

Page 26: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Similar grossly: • Splenomegaly • Red to purple • Oozes blood on cut surface

Active hyperemia

• Acute systemic infection

Passive congestion

• Vascular pooling (shock) • Barbiturate administration** • Hemolytic anemia

College of Veterinary Medicine, University of Illinois

Spleen – Circulatory disturbances

Page 27: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Splenic congestion from barbiturate euthanasia in a horse – marked splenomegaly

Histology: Red pulp dilated and contains blood; the white pulp is widely separated

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

Spleen – Circulatory disturbances

Page 28: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Gross Lesions: Acutely: infarcts are

discrete, raised, and

dark red – at the

margins of the organ

With time: pale and firm

(fibrosis)

} Due to thrombosis

Spleen – Circulatory disturbances

Splenic Infarcts: Ischemic necrosis of the spleen

1. Vascular damage

2. Hypercoagulable states

3. Splenomegaly (of any cause)

4. Septic emboli

Page 29: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Gross: Red nodular mass. Often very large, soft and dark red on cut surface

Splenic hematoma

• Common in dogs • Trauma • Often associated with nodular

hyperplasia or vascular tumours

Need histology to

rule out underlying

neoplasia!

Spleen – Circulatory disturbances

Page 30: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Spleen – Inflammation

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

• Older lesions resemble granulomas/abscesses

Tularemia, hepatitis and splenitis in a beaver

Images courtesy of Dr Daoust

Yersinia, lymphadenitis in a beaver

Acute splenitis – Multifocal necrosuppurative splenitis

Tularemia (Francisella tularensis)

Yersiniosis (Yersinia pseudotuberculosis)

Page 31: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Acute splenitis – Septicemic splenitis

• African swine fever • Erysipelas • Anthrax**

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

Spleen from a pig

Spleen – Inflammation

Page 32: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Acute splenitis – Septicemic splenitis - ANTHRAX

• A disease caused by a spore forming bacterium: Bacillus anthracis

• Zoonotic

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

• In ruminants – septicemic disease

Spleen – Inflammation

Page 33: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Anthrax – Pathogenesis in ruminants:

Ingestion / wound contamination / inhalation of spores

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

Spleen – Inflammation

Page 34: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Spleen – Inflammation

Anthrax - Lesions in ruminants

Page 35: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Spleen – Inflammation

Anthrax - Lesions in ruminants

Characteristic Findings:

• Bloated autolysed carcass with blood oozing from the orifices

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

• Take a blood smear from the ear!

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

Page 36: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

• 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?

Anthrax - Lesions in ruminants

Spleen – Inflammation

Page 37: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

• Diffuse granulomatous splenitis:

• Nodular granulomatous splenitis:

Chronic splenitis: Granulomatous splenitis

Mycobacterium avium infection in a chicken

Dept of Veterinary Biosciences, The Ohio State University

Histoplasmosis in a dog

Spleen – Inflammation

Images: Dr Fenton

Page 38: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Growth disturbances

Aplasia

Atrophy

Benign nodular hyperplasia

Lymphoid hyperplasia

Hyperplasia of the monocyte-macrophage system

Extramedullary hematopoiesis

Spleen – Disturbances of growth

Page 39: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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, University of Tennessee

Gross: Gray to red nodular mass(es): composed of lymphoid tissue and red pulp

Spleen – Disturbances of growth

Page 40: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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 41: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Histiocytic sarcoma, dog

* Covered in primary hematopoietic neoplasia

Primary splenic neoplasia Lymphoproliferative 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 42: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Cornell Veterinary Medicine

Splenic hemangioma

• Benign tumour of endothelial origin

This looks very similar to splenic hematoma and hemangiosarcoma! Histology is necessary!

Gross: Single, soft, dark red nodular mass

Spleen – Primary neoplasia

Page 43: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Splenic hemangiosarcoma

• Most common malignant tumour of the canine spleen

Gross:

• Single to multiple, discrete to coalescing masses

• Often dark red

• +/- metastases

Spleen – Primary neoplasia

Page 44: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Splenic hemangiosarcoma

• Most common malignant tumour of the canine spleen

Histology:

• Blood-filled vascular spaces lined by anaplastic endothelial cells

Spleen – Primary neoplasia

Page 45: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

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

• Often there are concurrent masses in the right auricle and liver

Splenic hemangiosarcoma

• Most common malignant tumour of the canine spleen

Spleen – Primary neoplasia

Page 46: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Metastatic splenic tumours: dog with pancreatic carcinoma

Spleen – Secondary (metastatic) neoplasia

Page 47: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Red Splenic Nodules

Splenic nodules

Hematoma

Hemangioma

Hemangiosarcoma

Splenic infarcts

Incompletely contracted areas of the spleen

Nodular hyperplasia (not always red)

Page 48: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Diffuse splenomegaly with a firm consistency = Meaty Spleens

Septicemia • Salmonella

Hemolytic disease

Lymphoma

Mast cell neoplasia

Histiocytic sarcoma

Granulomatous disease • Histoplasmosis

Amyloidosis

Diffuse Splenomegaly

Diffuse splenomegaly with a bloody consistency = Bloody Spleens

Septicemia • Anthrax, Salmonella

Acute hemolytic anemia

Splenic torsion

Barbiturate euthanasia*

Page 49: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Tonsils and Mucosa-Associated Lymphoid Tissue (MALT)

Tonsil Lymphoma in a dog

Tonsillitis in a pig • Subject to similar

disease processes as the LNs

• Constantly stimulated

• Important site of entry for pathogens

Page 50: Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L3-13_Shannon.pdf · –Composed of epithelial tissue and lymphoid tissue ... •Primary - trauma •Secondary

Questions?