pathology of the hematopoietic systempeople.upei.ca/smartinson/hemat-l2-12_shannon.pdf ·...
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Shannon Martinson, March 2012
Pathology of the Hematopoietic
System
Lecture 2: Lympho and
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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• Common benign skin masses in dogs
• Surgical excision usually curative
Plasma cell tumors
1. Cutaneous plasmacytoma
2. Extramedullary
plasmacytoma
• Arising at sites other than BM / skin
• Often affect the GI tract
• More aggressive, may metastasize
to the lymph nodes
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Plasma cell tumors
3. Multiple myeloma
• Malignant tumour of plasma cell origin arising in the bone marrow
• Uncommon in domestic animals: dogs > cats
• Neoplastic (clonal) plasma cells secrete immunoglobulin leading to hypergammaglobulinemia:
• Monoclonal gammopathy on serum electrophoresis
• Hyperviscosity syndrome
• Bence-Jones proteinuria
Normal Cat Serum
Monoclonal gammopathy
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Plasma cell tumors
3. Multiple myeloma
• Gross: Pale pink to dark red gelatinous masses
replace bone marrow – typically multiple masses!
• Histologically: Sheets of round cells– with
plasmacytoid morphology
Masses may occur in any bone, but most often occur in the vertebrae
Can see hypercalcemia due to ↑ osteoclastic activity
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Affected bones often
have “punched” out
appearance on
radiographs
Clinical diagnosis of multiple myeloma is based on finding 2 - 3 + of the
following features:
• Increased plasma cells in bone marrow (30%+)
• Punched out lesions on radiographs
• Monoclonal gammopathy
• Hypercalcemia
• Light chain (Bence-Jones) proteinuria
Plasma cell tumors
3. Plasma cell myeloma / Multiple myeloma
Courtesy of Dr. A Matthews, AVC
• Clinical signs: lameness, pain, lethargy, paraplegia
• Slowly progressive
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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
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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
• Flat-coated Retriever
• Can be solitary of multiple • Solitary lesions
• Surrounding joints, subcutis
• Lymph nodes, spleen or liver
• Multiple lesions • Disseminated histiocytic
sarcoma = malignant histiocytosis
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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)
Courtesy of Dr A Lopez, AVC
Histiocytic sarcoma, hilar and mesenteric lymph nodes
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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 – visceral mast cell tumours
• 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
Can see diffuse hepatic enlargement
• Primarily involves the
hematopoietic system
• Spleen, bone marrow
• Rare in animals: cats
• Gross: Splenomegaly +/-
nodular surface
Systemic mastocytosis – visceral mast cell tumours
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Myeloproliferative disease: Mast cell neoplasia
Histology:
Cords and sheets
of mast cells
efface the
parenchyma
Toluidine Blue
Systemic mastocytosis – visceral mast cell tumours
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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 A 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 and macrophages
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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Lymph circulation: • Afferent lymphatics subcapsular sinuses trabecular sinuses
medullary sinuses efferent lymphatics thoracic duct
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 and macrophages
Normal lymph node, cow
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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: Lymphadenopathy (lymphadenomegaly)
• Enlargement of the lymph node(s) of unknown cause
• Can be localized or generalized Lymphadenopathy
Enlargement of the right retropharyngeal LN sheep
Enlarged lymph nodes
Lymphadenitis*
Lymphoid hyperplasia* Hyperplasia of the monocyte/macrophage system
Primary neoplasia* Secondary neoplasia*
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• As opposed to reactive hyperplasia which is an antigen
driven immunologic response
Lymph node: Inflammation
• An inflammatory response to an infectious agent within the node Lymphadenitis
Acute Lymphadenitis
• Usually the result of a
regional lymph node
draining a site of
inflammation and
becoming infected
Cervical and sternal lymphadenitis with sepsis
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Lymph node: Acute lymphadenitis
Gross lesions:
• Enlarged, soft, wet, red lymph nodes
• Often bulging and hyperemic on cut surface
• Exudates are usually serous or hemorrhagic
Mesenteric lymphadenitis Popliteal lymphadenitis
Courtesy: Dr C Legge
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Lymph node: Chronic lymphadenitis
• With chronicity the
lymph nodes
become large,
irregular, and firm
due to fibrosis
• Chronic suppurative
lymphadenitis
• Chronic
granulomatous
lymphadenitis
Rhodococcus equi in a foal
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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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• 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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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
Image source unknown
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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**
Lymph node: Chronic suppurative lymphadenitis
Caseous lymphadenitis: Corynebacterium pseudotuberculosis
With time, there may be systemic
involvement with abscesses in the
internal organs
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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
Bovine Tuberculosis: Mycobacterium bovis
Lymph node: Nodular granulomatous lymphadenitis
Image: Cornell Veterinary Medicine
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• Histology: Granulomas with central necrosis and
mineralization surrounded by epithelioid macrophages and
multinucleated giant cells
Lymph node: Nodular granulomatous lymphadenitis
Bovine Tuberculosis: Mycobacterium bovis
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Lymph node: Nodular granulomatous lymphadenitis
Bovine Tuberculosis: Mycobacterium bovis
• Histology: Granulomas with central necrosis and
mineralization surrounded by epithelioid macrophages and
multinucleated giant cells
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Lymph node: Nodular granulomatous lymphadenitis
Bovine Tuberculosis: Mycobacterium bovis
Acid fast bacilli within macrophages
• Histology: Granulomas with central necrosis and
mineralization surrounded by epithelioid macrophages and
multinucleated giant cells
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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
Gross:
• Moderate
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
Supramammary LN
Reactive lymphoid hyperplasia Normal lymph node
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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
Lymph node: Neoplasia
Covered in primary hematopoietic neoplasia*
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• 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
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Metastasis of mammary
carcinoma to a lymph node
Lymph node: Secondary neoplasia
Images: Courtesy of Dr Hanna, AVC
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Questions?