Pathology of the lymphoid system Flashcards

1
Q

Primary lymphoid organs

A
  • thymus
  • bone marrow
  • bursa of Fabricius (birds)
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2
Q

Secondary lymphoid organs

A
  • spleen
  • LN
  • hymn nodules (e.g. MALT)
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3
Q

What happens in the primary lymphoid organs?

A
  • lymphocyte development
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4
Q

What happens in secondary lymphoid organs?

A
  • lymphocytes respond to antigens
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5
Q

Do lymphocytes continually recirculate?

A
  • yes
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6
Q

What is HEV?

A

= high endothelial venues
- specialised cuboidal endothelial cells that facilitate receptor-mediated transmigration of lymphocytes from blood

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7
Q

Does the spleen have lymphatic drainage?

A
  • no
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8
Q

Drainage / flow of lymphocytes within a lymph node

A
  • multiple afferent lymphatic vessels -> drain into subcapsular sinus -> trabecular sinuses -> medullary sinuses -> efferent lymphatic vessels
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9
Q

How do the majority of lymphocytes enter LNs?

Where do the remainder enter?

A
  • 90-95 enter through HEVs
  • the remaining enter through the lymphatic circulation
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10
Q

What are the 10 lymphosomes

A
  1. sub-mandibular
  2. parotid
  3. dorsal superficial cervical
  4. axillary
  5. medial iliac
  6. lateral sacral
  7. hypogastric
  8. popliteal
  9. superficial inguinal
    10.ventral superficial cervical
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11
Q

Indications to investigate a LN

A
  • LN enlargement (isolated or generalised)
  • suspect of an underlying infectious dz (e.g. Leishmania, FIP, fungi)
  • stage malignant neoplastic dz
  • provide material for molecular testing
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12
Q

FNA key points from LNs

A
  • avoid aspiration of the centre of markedly enlarge LN as often necrotic
  • spread gently
  • non-suction technique to minimise blood contamination
  • keep cytologic preparations away from formalin fumes
  • ideally take sample before giving steroids
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13
Q

What does a normal LN look like?

A
  • small lymphocytes (1-1.5xRBC) -> ~90%
  • medium (2-2.5xRBC) and large (>3xRBC) -> <5-10%
  • plasma cells, macrophages, mast cells, neutrophils -> rare
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14
Q

4 causes of lymphadenopathy

A
  • reactive hyperplasia
  • lymphoma
  • lymphadenitis
  • metastatic neoplasia
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15
Q

Is reactive hyperplasia localised or systemic?

A
  • can be either
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16
Q

Causes of reactive hyperplasia

A
  • antigenic stimulation
  • infectious causes
  • immune-mediated dz
  • neoplasia
  • vaccination
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17
Q

Reactive hyperplasia cytology

A
  • cytologically can be indistinguishable from normal LN
  • heterogenous cell population
  • small lymphocytes are predominant
  • may see increase in intermediate and large lymphocytes (up to 15-20%)
  • may see increased numbers of plasma cells (up to 5-10%)
  • occasional macrophages (~2%)
  • very few neutrophils, eosinophils, mast cells
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18
Q

What is lymphadenitis?

A
  • accumulation of inflammatory cells
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19
Q

Causes of neutrophilic lymphadenitis

A
  • bacterial
  • immune-mediated
  • neoplastic
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20
Q

Causes of eosinophilic lymphadenitis

A
  • hypersensitivity reaction
  • parasites
  • idiopathic
  • paraneoplastic (e.g. MCT, lymphoma)
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21
Q

Causes of macrophagic/granulomatous lymphadenitis and pyogranulomatous lymphadenitis

A
  • chronic inflammatory conditions (e.g. fungal infection, mycobacteriosis, leishmaniasis, FIP)
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22
Q

When do you classify lymphadenitis as neutrophilic?

A
  • > 5% neutrophils
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23
Q

When do you classify lymphadenitis as eosinophilic?

A
  • > 3% eosinophils
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24
Q

When do you classify lymphadenitis as macrophages?

A
  • > 3% macrophages
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25
What is lymphoma?
- neoplasia of lymphocytes in solid tissues
26
Subtypes of lymphoma
- anatomic site (e.g. multicentric, GI, cutaneous) - location of neoplastic cells within the LN (e.g. diffuse, follicular, T zone) - cell morphology (small, large, granular) - cell type (T-cell, B-cell, NK) - biological behaviour (indolent, aggressive)
27
Which cell affected by lymphoma has a better prognosis?
- B (best) - T (terrible)
28
What is the precursor for B cell lymphoma?
- lymphoblastic leukaemia or lymphoma
29
What is the precursor for T cell / NK cell lymphoma?
- lymphoblastic leukaemia or lymphoma
30
Examples of mature (peripheral) subtypes of B cell lymphoma
- small lymphocytic lymphoma/CLL - pro lymphocytic leukaemia - mantle cell lymphoma - marginal zone lymphoma (nodal, spleen, MALT) - follicular lymphoma - lympoplasmacytic lymphoma (inc. Waldenstrom macroglobulinaemia) - plasma cell neoplasms; myeloma, plasmacytoma - diffuse large B-cell lymphoma (including TCRBCL) - mediastinal (thymic) lymphoma - primary effusion lymphoma
31
What does TCRBCL stand for?
- t-cell-rich B-cell lymphoma
32
Examples of mature (peripheral) subtypes of T/NK cell lymphoma
- granular lymphocytic leukaemia or lymphoma - prolymphocytic leukaemia - adult t-cell leukaemia/lymphoma - hepatosplenic T-cell lymphoma - subcutaneous panniculitis-like lymphoma - mycosis fungoides/Sezary syndrome - peripheral t-cell lymphoma - angioimmunoblastic t-cell lymphoma - anglocentric t-cell lymphoma - anapaestic large cell lymphoma - aggressive NK cell leukaemia/lymphoma
33
Staging of lymphoma
1. Anatomic site a. generalised b. alimentary c. thymic d. skin e. leukaemia (true) (only blood and bone marrow involved) f. others (inc. solitary renal) 2. stage (to include anatomic site) I. involvement limited to a single node or lymphoid tissue in a single organ (excluding bone marrow) II. involvement of many LNs in a regional area (± tonsils) III. generalised LN involvement IV. liver and/or spleen involvement (± stage III) V. manifestation in the blood and involvement of bone marrow and/or other organ system (± stage I-IV) Each stage is subclassified into: a. without systemic signs b. with systemic signs
34
Use of histopathology and cytology for lymphoma
- cytology can be used for diagnosis and staging - accuracy of cytology decreases when we attempt to apply the WHO classification - histology is invasive, time consuming and more expensive - cytology combined with ancillary tests (e.g. flow cytometry, immunocytochemistry, PARR) → acceptable compromise in practice
35
Lymphoma - cytological findings
- homogenous appearance - most commonly increased percentage (>50%) of large immature lymphocytes - may see more mitoses than reactive - frequent lymphoglandular bodies (cell fragility -> not pathognomonic) - tingible bodies macrophages
36
Metastatic neoplasia - cytological findings
- LN may be reactive (i.e. reactive hyperplasia) - presence of cells not normally found in lymph nodes (e.g. carcinoma, sarcoma) - increased numbers of cells normally present often with atypical morphology (e.g. mast cells)
37
What is the capsule of the spleen rich in?
- elastic fibres and smooth muscle
38
What is the use of the red pulp of the spleen?
- reservoir of blood
39
What does the white pulp of the spleen contain?
- splenic lymphoid tissue (antigen presenting cells, macrophages, B & T lymphocytes)
40
Function of splenic capsule
- contraction can release blood (e.g. in response to acute blood loss)
41
Function of splenic red pulp
- reservoir of blood - filter for senescent or damaged erythrocytes - iron metabolism
42
Function of splenic white pulp
- immunity against bloodborne antigens
43
When is it indicated to investigate the spleen?
- diffuse or symmetrical enlargement - nodular or focal lesions - abnormal US appearance - evaluation of haematopoiesis - diagnosing neoplasia - tumour staging Often incidental finding
44
What does a normal spleen look like?
- similar to normal lymph node but typically more blood - neutrophils in blood proportions - small lymphocytes (1-1.5 x RBC) → ~ 90% - medium (2-2.5 x RBC) and large (>3 x RBC) → < 5-10% - plasma cells, macrophages, mast cells → rare
45
5 causes of splenomegaly
- reactive hyperplasia - splenitis - lymphoma - metastatic neoplasia - extra medullary haematopoiesis
46
Possible clinpath findings of infection/inflammation
- inflammatory leucogram - hyperglobulinaemia - infectious agent (e.g. Leishmania, Toxoplasma)
47
Possible clinpath findings of extra medullary haematopoiesis
- anaemia or other cytopenias seen on CBC
48
Possible clinpath findings of haemolymphatic neoplasia (e.g. lymphoma, multiple myeloma)
- lymphocytosis, atypical cells in circulation, cytopenias seen on CBC - hyperglobulinaemia, monoclonal gammopathy, paraproteinuria
49
Possible clinpath findings of other neoplasia (e.g. histolytic sarcoma, haemangiosarcoma)
- egenerative anaemia +/- other cytopenias, schistocytes, acanthocytes, thrombocytopenia
50
Possible clinpath findings of circulatory disturbances (e.g. haematoma, torsion, splenic congestion)
- regenerative anaemia, abnormal liver values, inflammatory/stress leucogram
51
Cytological findings of haematoma
- blood - haemoglobin breakdown products (haemosiderin - blue, haematoidin - yellow & rhomboid)
52
Thymus - structure, location, components
- Primary lymphoid organ → development of T lymphocytes - Located in the cranial mediastinum - Prominent before puberty → replaced by adipose tissue - 2 most important components: epithelial cells and lymphocytes (CD4+ CD8+)
53
2 main conditions affecting the thymus
- thymoma - lymphoma
54
Why is it important to distinguish thymoma from lymphoma?
Different origin - Thymoma → epithelial cells - Lymphoma → lymphocytes Different treatment - Thymoma → surgical treatment - Lymphoma → chemotherapy
55
How to diagnosis thymoma/lymphoma
- Imaging → mass in the cranial mediastinum - Cytology +/- flow cytometry (lymphocytes will be CD4+ and CD8+ if thymoma) - Definitive diagnosis: histopathology - Paraneoplastic syndrome: hypercalcaemia, myasthenia gravis
56
Thymoma - cytological findings
- epithelial cells - small lymphocytes - occasional mast cells
57
Lymphoma - cytological findings
- typically large atypical lymphocytes
58
What is another common cause of lymphadenopathy of the submandibular LN?
- dental dz
59
Which LN do lymphomas usually affect 1st?
- typically starts at the cranial LN and extends to the caudal ones
60
Use of PARR
- PCR for antigen receptor rearrangements - mainly used when still doubt over whether it is a reactive or neoplastic process - tells us if the proliferation is clone or not (if clonal = neoplasia)
61
Haematology changes after splenic contraction
- increase in haemltocrit - increase in lymphocytes
62
What cell is the precursor to platelets?
- megakaryocyte