Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L2-11_Shannon.pdf ·...
Transcript of Pathology of the Hematopoietic Systempeople.upei.ca/smartinson/Hemat-L2-11_Shannon.pdf ·...
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Shannon Martinson, March 2011
Pathology of the Hematopoietic
System
Lecture 2: Myeloproliferative diseases
Lymph nodes
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Hematopoietic Neoplasia
Lymphoproliferative Disease
Lymphoma
Lymphoid leukemia
Plasma cell tumours
Myeloproliferative
Disease
Histiocytic Neoplasia
Myeloid leukemia
Myelodysplastic Syndrome
Mast cell tumour
Primary Hematopoietic Neoplasia
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Hematopoietic Neoplasia
Lymphoproliferative Disease
Lymphoma
Lymphoid leukemia
Plasma cell tumours
Myeloproliferative
Disease
Histiocytic Neoplasia
Myeloid leukemia
Myelodysplastic Syndrome
Mast cell tumour
Primary Hematopoietic Neoplasia
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Myeloproliferative disease:
Histiocytic neoplasia/proliferative disorders
1. Cutaneous histiocytoma
• Common benign skin mass• Young dogs• Spontaneously regress
2. Reactive histiocytosis
• Immunoregulatory disease• Waxing and waning , progressive
• Cutaneous histiocytosis• Affects the skin
• Systemic histiocytosis• Affects skin and viscera
http://vetmedicine.about.com/od/diseasesandconditions/tp/Lumps-Bumps.htm
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Myeloproliferative disease:
Histiocytic neoplasia/proliferative disorders
3. Histiocytic sarcoma
• Malignant neoplasia of macrophage or dendritic cells
• Breed predispositions • Bernese Mountain dog
• Rottweiler
• Can be solitary of multiple • Solitary lesions
• Surrounding joints, subcutis
• Lymph nodes, spleen or liver
• Multiple lesions• Disseminated histiocytic
sarcoma = malignant histiocytosis
www.dkimages.com/discover/previews/1009/50211777.JPG
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Myeloproliferative disease: Histiocytic sarcoma
• Aggressive multisystemic disease
• Tumour masses in several organs:
spleen*, bone marrow*, lymph
nodes*, lung, skin
• Splenomegaly, hepatomegaly
3. Disseminated histiocytic sarcoma (= malignant histiocytosis)
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Myeloproliferative disease: Histiocytic sarcoma
• Histology: Masses / diffuse infiltrates composed of atypical histiocytes
• May be avidly hemophagocytic causing a non-regenerative anemia
3. Disseminated histiocytic sarcoma (= malignant histiocytosis)
Hemophagocytic histiocytic sarcoma
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Myeloproliferative disease: Mast cell neoplasia
• Common skin tumours of dogs
Cutaneous mast cell tumours
• Involves primarily the hematopoietic
organs
• Intestinal or gastric masses
Systemic mastocytosis
Alimentary mast cell tumour
Mast cells are widely distributed in the connective tissues -however they originate in bone marrow
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Myeloproliferative disease: Mast cell neoplasia
Systemic mastocytosis
• Primarily involves the
hematopoietic system
• Spleen, bone marrow
• Rare in animals: cats
• Gross: Splenomegaly +/-
nodular surface
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Myeloproliferative disease: Mast cell neoplasia
• Primarily involves the
hematopoietic system
• Spleen, bone marrow
• Rare in animals: cats
• Gross: Splenomegaly +/-
nodular surface
Systemic mastocytosis Can see diffuse hepatic enlargement
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Myeloproliferative disease: Mast cell neoplasia
Systemic mastocytosis
Histology:
Cords and
sheets of mast
cells efface the
parenchyma
Toluidine Blue
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Secondary bone marrow neoplasia
• Results of metastasis of a tumour from a distant site to the bone marrow
• Can be a carcinoma or a sarcoma
Courtesy of Dr Alfonso Lopez
Metastasis of a malignant pheochromocytoma to the rib, dog
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Myelophthisis
• Fibrosis → Myelofibrosis
• Neoplastic cells → leukemia, lymphoma, histiocytic sarcoma etc.
• May result in pancytopenia due to competition for space/nutrients
Dog: Replacement of bone marrow by lymphoma
• Replacement of hematopoietic tissue within the bone marrow by abnormal tissue Myelophthisis
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Lymphoid Tissue: Lymph nodes
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Lymph nodes
Function: • Filtration of lymph • Immune response
Structure:• Outer cortex follicles
(mostly B cells)• Inner cortex
paracortex (mostly T cells)
• Medulla mostly B cells
Lymph circulation:• Afferent lymphatics subcapsular sinuses trabecular sinuses
medullary sinuses efferent lymphatics thoracic duct
Modified from Pathologic Basis of Veterinary Disease
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Function: • Filtration of lymph • Immune response
Structure:• Outer cortex follicles
(mostly B cells)• Inner cortex
paracortex (mostly T cells)
• Medulla mostly B cells
Lymph circulation:• Afferent lymphatics subcapsular sinuses trabecular sinuses
medullary sinuses efferent lymphatics thoracic duct
Lymph nodes
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Lymph nodes
Function: • Filtration of lymph • Immune response
Structure:• Outer cortex follicles
(mostly B cells)• Inner cortex
paracortex (mostly T cells)
• Medulla mostly B cells Noah’s Arkive
Normal lymph node, cow
Lymph circulation:• Afferent lymphatics subcapsular sinuses trabecular sinuses
medullary sinuses efferent lymphatics thoracic duct
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Lymph node: General response to injury
Enlarged lymph nodes
Lymphadenitis
Lymphoid hyperplasia
Hyperplasia of the monocyte/macrophage system
Primary neoplasia
Secondary neoplasia
Small lymph nodes
Lymphoid atrophy
Lymph node degeneration
Lymph node hypoplasia
Two basic responses: Decrease in size or increase in size
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Lymph node: Decrease in size
Lesions:
• Gross:
• Small lymph nodes
• Histology
• Lymphoid depletion /
degeneration
Small lymph nodes
Lymphoid atrophy• Aging• Cachexia/malnutrition
Lymph node degeneration• Toxins• Chemotherapy• Viral infections
Lymph node hypoplasia
• Bovine Viral Diarrhea Virus• Feline Immunodeficiency Virus• Canine Distemper Virus• Feline and Canine Parvovirus
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Lymph node: Hemorrhage
• Originate within the lymph node or in the tissues drained by the node
Lymph node: Anthracosis
• Carbon within phagocytesBlack discolouration
Lymph node: Pigmentary changes
Red discolouration
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Lymph node: Lymphadenopathy (lymphadenomegaly)
Enlarged lymph nodes
Lymphadenitis
Lymphoid hyperplasia
Hyperplasia of the monocyte/macrophage system
Primary neoplasia
Secondary neoplasia
• Enlargement of the lymph node(s) of unknown cause
• Can be localized or generalizedLymphadenopathy
Enlargement of the right retropharyngeal LN sheep
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• As opposed to reactive hyperplasia which is an antigen
driven immunologic response
Acute Lymphadenitis
• Usually the result of a
regional lymph node
draining a site of
inflammation and
becoming infected
Lymph node: Inflammation
• An inflammatory response to an infectious agent within the nodeLymphadenitis
Courtesy: Dr. Legge
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Lymph node: Acute lymphadenitis
Gross lesions:
• Enlarged, soft, wet, red lymph nodes
• Often bulging & hyperemic on cut
surface
• Exudates are usually serous
Mesenteric lymphadenitis Tracheobronchial lymphadenitis
Dr McGavin, College of Veterinary Medicine University of Tennessee
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Lymph node: Chronic suppurative lymphadenitis
• Gross lesions:
– Swollen lymph
node with pus-
filled center =
Lymph node
abscess
• Response to
pyogenic bacteria
• Can fistulate to the
skin surface
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http://www.que.at/images/pferde/Durse/strangles.jpg
• Streptococcus equi subsp equi
• Inflammation of the URT → abscesses in the mandibular, retropharyngeal and parotid Lnn
• May fistulate to the surface
• Can spread to the viscera → “Bastard Strangles”
Equine
Strangles
Lymph node: Chronic suppurative lymphadenitis
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Porcine jowl abscess • Streptococcus
porcinus
• Colonizes oral
cavity/tonsils and
spreads to the
mandibular lymph
nodes
Lymph node: Chronic suppurative lymphadenitis
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Pathogenesis:
• Usually enters via contamination of shear wounds; rarely by inhalation
• Drains to regional lymph nodes
– Superficial nodes more often affected than internal nodes
• Prescapular LN
• Prefemoral LN
Caseous lymphadenitis: Corynebacterium pseudotuberculosis
• Chronic suppurative lymphadenitis in sheep & goats
• Ulcerative lymphangitis in horses and cattle
• Pectoral abscesses in horses
Lymph node: Chronic suppurative lymphadenitis
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Goat, caudal mediastinal
lymph nodes: lymph
node abcesses
Lymph node: Chronic suppurative lymphadenitis
Caseous lymphadenitis: Corynebacterium pseudotuberculosis
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• Chronic suppurative inflammation, caseous necrosis & fibrosis
• As lesion progresses characteristic concentric laminations**
In some cases there is
systemic involvement with
abscesses in the organs: especially the lungs
Lymph node: Chronic suppurative lymphadenitis
Caseous lymphadenitis: Corynebacterium pseudotuberculosis
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Nodular granulomatous lymphadenitis
Mycobacterium bovis
Mycobacterium avium subsp. paratuberculosis
Actinobacillus lignieresii
Migrating parasitic larva
Diffuse granulomatous lymphadenitis
Porcine Circovirus type 2
Histoplasma capsulatum
Blastomyces dermatitidis
Cryptococcus neoformans
• Focal or multifocal
• Often white-yellow nodules
• +/- caseous necrosis/mineralization
• Enlarged, pale, dry, firm
lymph nodes
• Loss of architecture
Lymph node: Granulomatous lymphadenitis
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• Gross: Enlargement of the lymph node with multiple
discrete yellow-tan gritty (caseated) nodules
Image: Noah’s Arkive
Bovine Tuberculosis: Mycobacterium bovis
Lymph node: Nodular granulomatous lymphadenitis
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• Histology: Granulomas with central necrotic debris
surrounded by epithelioid macrophages and multinucleated
giant cells
Image: Noah’s Arkive
Lymph node: Nodular granulomatous lymphadenitis
Bovine Tuberculosis: Mycobacterium bovis
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• Histology: Granulomas with central necrotic debris
surrounded by epithelioid macrophages and multinucleated
giant cells
Image: Noah’s Arkive
Lymph node: Nodular granulomatous lymphadenitis
Bovine Tuberculosis: Mycobacterium bovis
Acid fast bacilli within macrophages and MNGCs
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• Gross: Diffuse enlargement of the mesenteric lymph nodes
Postweaning multisystemic wasting syndrome (PMWS): Porcine Circovirus type 2
Lymph node: Diffuse granulomatous lymphadenitis
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• Histology: Granulomatous infiltration of the node with large
botryoid intracytoplasmic viral inclusions
Postweaning multisystemic wasting syndrome (PMWS): Porcine Circovirus type 2
Lymph node: Diffuse granulomatous lymphadenitis
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Benign reactive hyperplasia
Cornell Veterinary Medicine
Gross:
• Enlargement of the
node(s)
= Lymphadenopathy
• May bulge on cut
section
Lymph node: Hyperplasia
• Can be localized or generalized
• Immunological reaction = response to antigen presentation or
circulating interleukin levels
–Lymph nodes draining site of local infection or vaccination
–Also occurs during early stages of lymphadenitis
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Histology:
• Proliferation of lymphoid follicles with prominent germinal centers*
• Increased T cells in the paracortex
• +/- Increased plasma cells in the medullary cords
Lymph node: Hyperplasia
Antigenic stimulation
*
*
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Primary lymph node neoplasia = Lymphoma
Covered in primary hematopoietic neoplasia*
Lymph node: Neoplasia
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• Lymph node metastasis:
• Common with carcinomas, melanomas, mast cell tumors,
etc.
• 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
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Metastasis of mammary
carcinoma to a lymph node
Lymph node: Secondary neoplasia
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Questions?