Lymph nodes - benign and malignant Flashcards
Differentiate nodular lymphocyte predominant Hodgkin lymphoma and classic Hodgkin lymphoma? 1 similarity.
Both have scarce neoplastic cells - lymphocyte predominant cells
Differentiate by type of malignant cells:
- Intact B cell lymphoma phenotype
- popcorn cells (nodular predominant)
Clinical history: lymphadenopathy
1 duration, rate of enlargement, pain
2 sore throat, cough, fever
3 fatigue, weight loss, pst history of malignancy
4 drugs, occupation, pets, travel
5 age: >50yrs increases risk of malignancy
Brief outline of the molecular pathogenesis of follicular lymphoma?
1 Translocation: t(14;18)
2 increased bcl-2 expression
3 decreased apoptosis and B cell accumulation in absence of Ag
4 further genetic insults (I.R1 T cell signature, better prognosis or I.R2 monocyte signature, worse prognosis)
What happens in follicle germinal centre formation?
Selection and amplification of very high affinity antigen B cells
Differentiate into:
- plasma cells (antibody)
- memory cells (long lived)
Lymphadenopathy pathology tests ()
1 FBC - atypical lymphocytes, neutrophilia, leukaemia/lymphoma
2 culture - throat or wound swab
3 serology - EBV, CMV, HIV, toxoplasma, autoimmune
4 imaging - CXR, US, CT/MRI
5 biopsy - excision, fine needle aspiration (ALWAYS include flow cytometry), core biopsy
Non Hodgkin Lymphoma aetiology
- poorly understood
- causes unknown for most BUT H. Pylori well described for minority
- No. of risk factors well understood
What is the cause of lymph node enlargement?
Encountering a pathogenic antigen and mounting an adaptive immune response = rapid proliferation
Secondary lymphoid tissue and role (3)
Role: All secondary lymphoid tissues contain mature lymphocytes capable of recognising Ag.
1 lymph nodes
2 spleen
3 MALT (tonsil’s, adenoids and Peyer’s patches)
Primary lymphoid tissue and role (2)
Bone marrow - B cell maturation + haemopoetic stem cells and lymphoid progenitor cells
Thymus - T cell maturation
2 types of oncogenic genetic errors?
1 chromosome translocations
2 errors in SHM
Multistep additional translocation, mutations lead to tumour progression and transformation
Definition of lymphoma (3 key points)
1 soft tissue neoplasm of lymphocytes
- overlap lymphocytic leukaemias
- collectively called lymphoproliferative disorders
2 all lymphomas are malignant
- inherent trafficking abilities of lymphocytes: other cancers acquire metastatic abilities
3 most (80%) arise in lymph nodes
Outline steps involved in the late primary immune response in a lymph node (5)
- with Th cells
1 Naive Th cell encounters Ag-APC
2 proliferation Ag primed Th cells
3 Ag primed Th - Ag primed B cell interaction
4 centroblastic transformation of B cell, proliferation
5 Follicle germinal centre formation
Non Hodgkin Lymphoma clinical categories ()?
Indolent (low grade)
- incurable, chronic relapsing
- median survival 10yrs
Agressive
- clinically agressive but curable for greater proportion
- rapidly enlarging nodes/extranodal mass (40%)
High grade
- younger patients
- curable
- extremely high growth rate: obstruction of vital organs
- rapid dissemination, leukaemia, CNS
Pathology of benign lymphedanopathy
Different causes provoke lymphoid proliferation and differentiation in different lymph node compartments
The lymph node compartment involved indicates predominant immune reaction
- follicular hyperplasia: suggests predominantly humoural
- paracortex hyperplasia: suggests cell mediated
Most lymph node enlargement involves >1 compartment
Define classic Hodgkin Lymphoma + age distribution
B cell derived lymphoma characterized by distinctive immunophenotype and relatively few malignant cells in a nonneoplastic inflammatory background
Bimodal age distribution: 15-35 and 50-70
Risk factors for non hodkin lymphoma
immunologic
- strongest
- immunosuppressed for organ transplant: high grade, extranodal + EBV
- HIV: high grade, extranodal + EBV
- congenital/primary immunodeficiency
- autoimmune disease (Rh.A, SLE, chronic Ag stimulation)
viral
- HIV
- EBV: integrates into B cell genome
- HCV/HHV8/HTLV1
genetic
- inherited immunodeficiency
environmental
- pesticides, herbicides, smoking, high fat/meat diet
Differentiate lymphoid follicles (2)
1 primary - mature, naive
2 secondary - follicular dendritic cells and Th cells differentiate mature lymphoid cells
Lymph node flow, histology and function:
Capsule of CT containing:
- cortex
- paracortex
- medulla
Capsule
- afferent lymphatic vessels drain into capsule
- subcapsular sinus
- into trabecular sinuses
TO lymph node proper (lymphocyte interaction)
- Cortex: lymphoid follicles, B cell zone
- Paracortex: T cell zone
- Medulla: cords (plasma cells) and sinuses (macrophages)
- leave lymph node via efferent lymphatic
- can enter another lymph node
Diagnostic procedures for lymphoma? (3)
Lymph node excision
- gold standard for Dx
Fine needle aspiration + flow cytometry
Needle core biopsy
- can see architecture of nodes
Most common T cell lymphoma?
Peripheral T cell lymphoma not otherwise specified
Define lymphoma in terms of disease (2)
Broad division:
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma (more commonly B cell (85%), and less commonly T cell (<15%))
Benign causes of lymphadenopathy (5)
1 Infection
2 Immunological diseases (e.g. rheumatoid arthritis, SLE)
3 Lipid storage diseases
4 Endocrine diseases (e.g. hyperthyroidism)
5 Other disorders (e.g. sarcoidosis, dermatitis)
Types of Hodgkin Lymphoma’s (2 types + 3 subtypes)?
Classic subtypes
- nodular sclerosis
- mixed cellularity
- lymphocyte - rich or depleted
Nodular lymphocyte predominant
T cells and MHC class (2)
1 Th and MHC II
2 Tc and MHC I
Why are B cell lymphomas more common than T cell lymphomas?
Mature T cells do not undergo further physiological mutation whereas B cells do (Ig and TCR rearrangement etc.)
Pathological diagnosis of lymphoma
1 Histology is mainstay
2 Immunophenotype: flow cytometry
3 Cytogenetics
4 Molecular studies
Definition of lymphoma according to what characteristics (6)?
Heterogenous group (>80%) of malignancies characterised by proliferation of lymphoid tissue diverse in:
- cellular origin
- morphology
- immunophenotype
- cytogenetic & molecular abnormalities
- response to treatment
- prognosis
Most common B cell lymphomas (2)?
Diffuse large B cell
Follicular
What clinical presentation is typical of a person with Hodgkin Lymphoma?
Non tender, peripheral lymphadenopathy + predictable spread to contiguous nodes
Asymptomatic OR
Fever, night sweats, weight loss
Fatigue and itching
Classic Hodgkin Lymphoma pathology: 3 cell types… which interact with one another
1 Reed Sternberg cells: derived from germinal centre B cells BUT deficient B cell phenotype
- rescued from apoptosis by NFkB
2 Mononuclear Hodgkin cells
3 Reactive cells: T cells, macrophages, eosinophils, plasma cells, neutrophils, fibroblasts
Suspicion inducing ‘flags’?
1 lymphadenopathy > 1 cm persisting for 6 weeks
2 hepatosplenomegaly
3 3 or more of following symptoms (FAWN, itching, breathlessness, bruising, recurrent infection, bone pain)
Early stage treatment of B-NHL (sIg+)?
may be selected for and dependent on Ag.
Example: gastric MALT lymphoma, treated with H. Pylori antibiotics
Outline steps involved in the primary immune response in a lymph node (5)
- without Th cells
1 Naive B cell encounters Ag
2 blastic transformation and proliferation
3 travel through medullary cords and differentiate into short lived plasma cells
4 Ab production
5 Ag-Ab complexes trapped by FDCs
Characteristics of a benign node (3)
1 hyperplastic - extend capsule = tenderness
2 neck, axilla and inguinal region, > 1.5cm and more in children
3 may be soft or firm (not hard or rubbery)
