Lymph Node Pathology Flashcards
List 3 examples of secondary lymphoid tissue
Lymph nodes
Spleen
MALT
What are some common sites of MALT?
Tonsils, adenoids
Along GIT
Airways
Describe the histological appearance of a naive B cell vs. an activated B cell
Naive: small, blue, not much cytoplasm
Activated: larger, different morphology
What is a primary follicle in the context of a lymph node?
A dense cellular aggregation composed of inactive small resting B cells (their condensed nuclear chromatin gives the follicle a blue colour)
What is a secondary follicle in the context of a lymph node?
Secondary follicles consist of a pale centre called the germinal centre, surrounded by a darker zone known as the mantle zone
What is the structure of the mantle zone?
The mantle zone is made up of small resting B cells, the condensed nuclear chromatin producing the dark blue colour
What is the role and structure of the germinal centre?
The germinal centre is the site of B cell activation, clonal expansion and differentiation and consists of dividing B cells which are larger and paler than the small inactive lymphocytes of the marginal zone
Describe the structures found in a lymph node
External fibrous capsule: oval, well-circumscribed
Afferent and efferent veins and arteries, as well as the efferent lymphatic vessel: enter and leave at the hilum
Afferent lymphatics: enter around the outside of the node through the capsule, bring in APCs and Ag (which then travel through to the B and T cell areas)
Veins and arteries: form sinuses (cortical and inner medullary) which percolate through the node
B and T cell areas (cortex and paracortex respectively)
Inner medulla: with medullary sinuses and extensions of the B and (mostly) T cell areas called the medullary cords
Medullary cords: final differentiation into plasma cells occurs here (immunoblasts can be seen)
What happens in a germinal centre and after?
Following appropriate stimulation by APCs or Ag, naive B lymphocytes from the mantle zone undergo clonal expansion and differentiation into centroblasts, centrocytes then immunoblasts. Somatic hypermutation and heavy chain class switching occur From the GC, the activated B cells migrate to the medullary cords where they complete their differentiation into plasma cells (or some cells become memory B cells)
What are the paler areas within the GC?
Macrophages containing phagocytosed apoptotic cells (called tingible body macrophages)
What other cells (besides B cells) are located within the GC?
FDCs
CD4 helper T cells
What conditions can cause a lymphadenopathy?
Reactive (inflammatory and infective): localised infection in the area of drainage, systemic infection (usually viral), non-infective systemic disease (e.g. RA, SLE), drugs
Neoplastic: lymphomas, leukaemic infiltration, metastases
When is a lymphadenopathy considered significant?
Dependent on age of patient and size of lymph nodes (generally cause for concern when <1-2cm)
What histological features are seen in an acute non-specific lymphadenitis?
Neutrophil infiltration
Oedema
Follicular hyperplasia
How does an acute non-specific lymphadenitis present and what is the most common cause?
Nodes are large and painful
Usually caused by microbial infection
What causes pain in a lymphadenitis?
Lymph node capsule contains pain fibres which are stimulated when the capsule is stretched
What are the 4 patterns of chronic non-specific lymphadenitis?
Follicular hyperplasia Paracortical Sinus histiocytosis Graulomatous inflammation Mixed pattern
What causes follicular hyperplasia in chronic non-specific lymphadenitis?
Stimuli that activate humoral immune responses (e.g. autoimmune disease, microbial infection)
What causes chronic paracortical lymphadenitis?
Stimuli that activate cellular immune responses (e.g. viral infections, certain drugs)
What causes sinus histiocytosis?
Increase in macrophages in sinuses, caused by a non-specific stimulus (e.g. draining cancers, infection)
What is a more common cause of neoplastic lymphadenopathy: primary or secondary tumours?
Secondary
What types of tumours readily metastasise to lymph nodes and which do not?
Many carcinomas, melanomas, germ cell tumours readily metastasise to lymph nodes
Sarcomas do not metastasise to nodes readily
What is classification of neoplastic proliferations of haemopoietic and lymphoid tissues based on?
Cell lineage
Morphology
Immunophenotypic profiles +/- genetic abnormalities
Clinical features (to some extent)
List 5 types of lymphoid neoplasms
Precursor B cell neoplasms
Precursor T cell neoplasms
Peripheral/mature B cell neoplasms
Peripheral/mature T cell and NK cell neoplasms
Hodgkin lymphoma (neoplasms of Reed Sternberg cells and their variants)
List 3 types of myeloid neoplasms
AML and related neoplasms
Myelodysplastic syndromes
Myeloproliferative neoplasms e.g. CML
What other types of haemopoietic and lymphoid tissue neoplasms are there besides lymphoid and myeloid?
Histiocytic and dendritic cell neoplasms
What is the difference between a leukaemia and a lymphoma?
Based on cell type the neoplasm resembles and the relative involvement of bone marrow and peripheral blood vs. tissues (e.g. CLL vs. small lymphocytic lymphoma respectively)
What is the universal B cell marker?
CD20
What is the universal T cell marker?
CD3
What is leukaemia?
Malignant neoplasm involving proliferation of haematolymphoid cells, mostly at a precursor stage, usually neoplastic cells spill over into blood +/- infiltrate other tissues
What is the difference between an acute and a chronic leukaemia?
Acute: abnormal cells show features of blasts, abrupt clinical onset, aggressive if not treated, present with bleeding, infections and anaemia
Chronic: abnormal cells are more mature, more indolent course
What is lymphoma?
Primary malignant neoplastic disease of lymphoid cells, mostly at a mature or post-bone marrow stage (peripheral)
Generally arise as more discrete masses in tissues outside of bone marrow but can involve bone marrow
No or minimal peripheral blood involvement
What are the 2 main groups of lymphomas and what differentiates them?
Hodgkin lymphoma: nodal origin only
Non-Hodgkin lymphoma: nodal or extranodal origin
List 4 risk factors for lymphoma
Immunosuppression/immunodeficiency: HIV, post-transplant, congenital immunodeficiency states
Some AI disease: Hashimoto’s thyroiditis
Infectious agents: EBV, H. pylori
Environmental: chemotherapy, radiation, chemical
What is the characteristic chromosomal translocation in most follicular lymphomas and what is its effect?
t(14;18)
Juxtaposition of IgH locus on Ch 14 with BCL2 locus on Ch 18 results in overexpression of the BCL2 anti-apoptotic protein
What is the characteristic chromosomal translocation in Burkitt’s lymphoma and what is its effect?
Part of Ch 8 with MYC oncogene is translocated to 1 of 3 Ig gene regions on other Chs, normally transcribed at a greater rate than MYC, leading to the over-expression of the c-MYC protein and therefore sustained growth promotion
What is the role of EBV infection in promoting lymphoma?
Infects B lymphocytes but is kept within its latent phase but T cells
Loss of T cell immunity allow expression of viral proteins which can activate signalling pathways leading to polyclonal B cell proliferation and ultimately lymphoma
What are the clinical features of lymphoma?
B symptoms: fever, night sweats, weight >10% from baseline in 6 months
How is lymphoma diagnosed? What features are examined?
Most accurately using a tissue biopsy
Looking at morphology (architecture and cytological features), immunohistochemistry (using panel of antigenic markers), +/- flow cytometry and genetic studies
What are the histological features of Hodgkin lymphoma?
Neoplastic cell referred to as Reed-Sternberg cell and variants
Neoplastic germinal centre B cells
Background of non-neoplastic lymphocytes and other inflammatory cells
How does a Reed-Sternberg cell appear?
Large cell with abundant cytoplasm and a larger bilobate nucleus with prominent eosinophilic nucleoli
When do many cases of Hodgkin lymphoma arise?
In young people (with a 2nd peak later in life)
How many histological types of Hodgkin lymphoma are there?
5: 4 classical Hodgkin lymphomas and a nodular lymphocyte predominant type
Where do Hodgkin lymphomas arise and spread to?
Initially enlargement of 1 LN group
May progress to involve adjacent LN groups and other lymphoid organs (e.g. spleen, bone marrow, liver)
Where do non-Hodgkin lymphomas arise and spread to?
Usually arise in lymphoid organs (e.g. LNs), but many are “extranodal”
Give examples of some extranodal origins of non-Hodgkin lymphomas
Thyroid in Hashimoto’s
Stomach in H. pylori gastritis
Other - e.g. brain, breast, lung, intestine
What are the 2 main groups of non-Hodgkin lymphomas? Which is more common?
B cell (85%) T cell
What is the most common B cell non-Hodgkin lymphoma?
Diffuse large B cell lymphoma
Contrast diffuse large B cell lymphoma with follicular lymphoma histologically
Diffuse large B cell lymphoma: recapitulate GC or post-GC B cells (centroblasts and immunoblasts)
Follicular lymphoma: recapitulate differentiating B cells within a GC, forming nodules/follicles, but the predominant cell type shows features of centrocytes
How is CLL differentiated from SLL?
Distinguished by presence/absence of lymphocytosis
Cells in both cases are mature-looking B lymphocytes of naive or memory cell type
What pattern of CD markers is seen in follicular lymphoma?
Surface Ig +ive
B cell antigens (CD19, CD20, others)
CD10+, CD5-, CD43-
What pattern of CD markers is seen in CLL/SLL?
Surface Ig weak
B cell antigens (CD19, CD20, others)
CD10-, CD5+, CD23+
