Lymph Nodes and Thymus Pathology

• Pathology of Lymph Nodes and Thymus is the study of diseases affecting these organs.

Traditional Division of Tissues

• Myeloid tissues include bone marrow and cells derived from it, such as red blood cells, platelets, granulocytes, and monocytes.
• Lymphoid tissues include the thymus, lymph nodes, and spleen, with the spleen being the largest lymphoid organ.

Lymphoid Cell Origins and Maturation

• All lymphoid cells originate in the bone marrow.
• B cells mature in the bone marrow.
• T cells migrate to the thymus to undergo differentiation.

Lecture Outline Topics

• Thymus: Congenital and acquired causes of hypoplasia, hyperplasia, associated conditions, and neoplasia.
• Lymph Nodes: Structure, functional compartments, classification of enlargement, and general inflammatory causes of enlargement.

Anterior Mediastinum

• The mediastinum is the thoracic cavity located between the pleural cavities, extending from the sternum to the spine and from the thoracic inlet to the diaphragm.

Thymus: Origin and Structure

• The thymus is embryologically derived from the 3rd (and sometimes 4th) pair of pharyngeal pouches.
• A fully developed thymus consists of two fused, well-encapsulated lobes.
• The thymus is populated by immature T lymphocytes (thymocytes) as major cells and thymic epithelial cells as minor cells.

Thymus: Function

• Progenitor cells migrate from the bone marrow to the thymus.
• The thymus matures these cells into T lymphocytes, able to distinguish between self and non-self antigens (self-tolerance).
• In immunology, an antigen is a molecule or molecular structure present on the outside of a pathogen, triggering an immune response.

Thymus Histology

• Photomicrographs show the thymus gland is lobulated by fibrous tissue.
• The dense, outer cortex is mainly composed of lymphocytes (thymocytes).
• A loose, inner medulla is mainly composed of epithelial cells.

Hassall Corpuscles

• Hassall corpuscles are round, keratinized formations with mature epithelial cells found in the medulla of the thymus gland.

Thymic Pathology

• Developmental issues include Agenesis and hypoplasia.
• Agenesis is the lack or failure of tissue/organ to develop.
• Hypoplasia is the underdevelopment of tissue/organ.
• An example of hypoplasia is DiGeorge syndrome, which causes severe defects in cell-mediated immunity and is due to a microdeletion on the long arm of chromosome 22.
• Acquired issues include atrophy, hyperplasia, and neoplasia which can lead to decrease in the # of cells.
• Atrophy refers to the decrease in size of tissue/organ.
• Hyperplasia refers to the increase in size of tissue/organ.
• Neoplasia refers to the abnormal growth of cells/tissue.

Acquired Thymic Atrophy

• Thymic mass varies with age:
  • Birth mass is approximately 15g
  • Puberty is ~35g
  • 25 years of age ~25g
  • 60 years < 15g
  • 70 years ~ 5g
• Reasons for changes of thymus size include: Age, Malnutrition, stress, terminal illness, and exposure to cytotoxic drugs.

Thymic Hyperplasia

• It refers to the appearance of reactive B-cell lymphoid Follicles
• Hyperplasia includes an increase in the number of follicles.
• Normally, there are small numbers of B-cell follicles present.
• Size of gland is independent
• Seen in chronic inflammatory states, or Immunologic states

Thymic Hyperplasia: Associated Diseases

• Associated diseases include:
  • Myasthenia Gravis: frequent with hyperplasia in 65-75% of cases and involves muscle weakness due to issues at the neuromuscular junction
  • Other autoimmune diseases, such as Graves' disease (thyroid), Addison's disease (adrenal cortex), systemic lupus erythematosus (SLE), scleroderma, and rheumatoid arthritis.
    • Graves (Goiter/Basedow): Most common cause of hyperthyroidism
    • Addison's disease (adrenal cortex): Insufficient production of cortisol and aldosterone
    • SLE: Immune system mistakenly attacks healthy tissue.
    • Scleroderma: Causes changes in the skin, muscles, internal organs, and blood vessels.
    • Rheumatoid arthritis: Inflammation of the joints.

Myasthenia Gravis

• It is a disease of the neuromuscular junction caused by autoantibodies directed against acetylcholine receptors (AChRs), leading to defective signal transmission across the synapse.
• Women under 40 are most commonly affected.
• Males = Females in older female population.

Myasthenia Gravis Clinical Features

• Symptoms includes Easy fatiguability, Ptosis, and Diplopia
• Easy fatiguability can cause double vision
• Ptosis causes drooping eye
• Diplopia can make A person see 2 images of one object
• The patient can see more acetylcholine or succinylcholine
• Symptoms worsen with repeated stimulation, such as increased use of affected muscles leading to decreased function.

Thymic Neoplasms

• A variety of neoplasms may arise in the thymus:
  • Thymomas of epithelial origin
  • Lymphomas of lymphoid origin
  • Other tumors such as endocrine cell tumors and germ cell tumors (teratomas).

Thymomas

• Thymomas are most common in the fifth and sixth decades of life.
• It is seen in 20% of patients with Myasthenia Gravis
• Occurs slightly more in females than males
• Neoplasms are derived from thymic epithelial cells:
  • Cytologically benign and noninvasive
  • Cytologically benign but biologically aggressive (invasive or metastatic)
  • Cytologically malignant which is a thymic carcinoma and very rare.
• Thymic epithelial tumors are staged according to the TNM system of tumour, nodal or metastasis.

Thymoma: Clinical Presentation

• Patients can be asymptomatic or symptomatic
• Symptoms are attributable to: - Mass pressure symptoms - Autoimmune diseases such as Myasthenia gravis - Complications of thymoma-associated immunodeficiencies - Paraneoplastic syndromes. It can also include systemic problems like fever, weight loss.
• The patient has a higher risk of developing second degree cancer

Lymphatic System

• Lymph nodes are major components of the lymphatic system.
• Lymph Nodes clustered in small groups, or chains at various strategic locations in the body.
• drains lymph from regions of the body through lymphatic vessels.

Lymph Node and Lymphoid Cell Functions

• All lymphoid cells originate in the bone marrow.
• B lymphocytes mature in the bone marrow (primary lymphoid organ).
• T lymphocytes migrate to and differentiate in the thymus (primary lymphoid organ).
• B and T lymphocytes colonize secondary lymphoid organs: lymph nodes, spleen and MALT (Mucosa-Associated Lymphoid Tissue).

Lymph Node Structure

• Function:
• To filter out foreign antigens.
• Site for recognition and processing of antigens.

Lymph Node Histology

• The architecture is composed of distinct interfacing compartments to process antigens, promote interaction, and cause an immune response.

Lymph Node Components

• Cortical area (superficial cortex): includes lymphoid follicles with their germinal centres and is the B-Cell rich area of the lymph node for humoral immunity.
• Paracortical area (deep cortex): densely cellular area beneath the cortex that extends BETWEEN the Lymphoid Follicles, includes lymphoid cells and postcapillary venules, it is the T-Cell rich area of the lymph node.
• Medullary area: it is the main site of plasma cell proliferation, differentiation, and production of antibodies.

Primary vs Secondary Lymphoid Follicles

• Primary lymphoid follicles are round nodules (1mm in diameter): They consist of small, darkly-staining, INACTIVE lymphocytes.
• Secondary-reactive lymphoid follicles are derived from antigens that are molecules that may be present on the outside of a pathogen and the areolar areas do not have the pale or active lymphocytes.
• Mantle zone – lymphocytes are all of B-cell type
• Germinal centers include a population of lymphoid cells in various stages of maturation and vary in size and enlarge in response to antigenic stimulation.

Reactive Lymphoid Follicles

• Secondary-reactive lymphoid follicles comprise a peripheral area, or mantle zone, of closely packed, small lymphocytes and centrally located pale germinal centers.
• Germinal centers include a population of lymphoid cells in various stages of maturation, histiocytes that are cells capable of ingesting debris, and other supportive cells with macrophages.

Lymphadenopathy

• Lymph node enlargement caused by infections, autoimmune diseases, or cancer.
• Reactive hyperplasia, or neoplasia If there are primary lymphomas or leukaemias or secondary metastases
• Enlargement such as in the case of breast cancer

Reactive Hyperplasia

• Reactive hyperplasia is nonspecific as various stimuli may cause the same reaction.
• Stimuli include microbes, cell debris, and foreign material.

Reactive Hyperplasia Process

• Involves antigen processing by macrophages and activation of resting/memory lymphocytes.
• Leading to morphological change (blast transformation) with ↑ size/cytoplasm and a more pallor with more cytoplasm. There is also inccreased presence of nucleoli & mitoses.
• This leads To in Secretion of Cytokines that promotes recruitment of other cells which then eliminate the pathogen with morphologic change.

B Lymphocyte Activation

• When B lymphocytes are exposed to an antigen it promotes a morphological change that is displayed in the lympth node and B cell count is increased..

T Cell Activation

• T cell activation occurs by eliminating the antigen.

Reactive Hyperplasia

• Histology varies with:
• Patient age
• Inducing factor
• Past Exposure
• Time/Duration
• Histologic pattern represents a POINT in the immune activation
• <8 days – paracortical/diffuse hyperplasia (T-Cell)
• 15> days – follicular hyperplasia (B-Cell)

Acute Reactive Hyperplasia

• Associated to presence of microbes which cause an immune resposne.
• Located in the tonsils, inguinal, or is Enteric.
• Generalized symptoms due to viral infections Bacteraemia, and Septicaemia

Acute Reactive Hyperplasia: Clinical Features

• Painful, in the lymph node the gross area has a red or grey color
• Intact Capsule ± perinodal extension
• Follicular hyperplasia, Sinusoidal congestion, and polymorphs ±is are Microscopic

Chronic Reactive Hyperplasia

• Activation of resident immune cells leads to morphological changes in the lymph nodes.
• Follicular (B cell): caused by stimuli that activate humoral immune responses.
• Paracortical/ diffuse (T cell): caused by stimuli that trigger (t-cell-mediated immune responses) e.g., viruses
• Sinus histiocytosis (macrophages): expansion of the lymphoid sinuses with increase in blood vessel cells and macrophages.

Lymph Node Histology

• Vary based on the type of reaction that can be Follicular , Interfolliccular or Sinusoidal.

Follicular Lymph Node Histology

• Parafollicle the B Cell, a Pale geminal centre Reactive follicular hyperplasia (may be serrated, serpentine or dumbbell shaped)
• It all relates to the chronic reactive response.
• reactive follicular hyperplasia containing numerous tingible-body macrophages containing dead cells and debris (starry-sky appearance) • no distinct follicles caused by virus in T-cell & expand compress the follides-

Paracortical Hyperplasia:

• It expands by increasing the number of lymphocytes (follicles not readily seen) with T-cell regions, typically containing immunoblasts, and activated cells 3 -4x the size of a resting lymphocyte with moderate amounts of pale cytoplasm, especially on the paracortex.

Summary

Thymus:

• It is primarily a lymphoid organ populated by mainly T-lymphocytes, it leads to hyperplasia and associated conditions e.g. MG (Myasthenia Gravis)
• Can have Thymus where lymph nodes can have a structure with functional compartments
• The can present with General inflammatory causes of Hodgkin's Lymphoma

Explore the pathology of lymph nodes and thymus, covering myeloid and lymphoid tissues. Learn about lymphoid cell origins, maturation, and key topics like thymus hypoplasia, lymph node enlargement, and mediastinum anatomy.