Pathology of the lymphoid system

• Primary lymphoid organs

  B and T lymphocytes proliferates, differentiate and mature, lymphocytes originate from stem cells in the bone marrow, then B lymphocytes typically continue to develop at this site; progenitor T-cells migrate from the bone marrow to mature and undergo selection.

  Includes the:

  • Thymus
  • Bone marrow
  • Bursa of Fabricus (birds)
• Secondary lymphoid organs

  Responsible for the immune responses to antigen (i.e. production of antibodies and cell-mediated immune reaction); they are organised to concentrate antigens, antigen presenting cells and lymphocytes in a way that helps interaction.

  Includes:

  • Spleen
  • Lymph modes
  • Lymph nodules (e.g. MALT).
• The circulation of the lymphoid system

  Lymphoid cells and other leucoytes move on a large scale. Lymphoid cells may move from tissue to lymph nodes via the afferent lymph and may subsequently leave that lymph node in the efferent lymphatic vessel. This discharges into the thoracic duct, which in turn drains into the blood circulation.
• The structure of lymph nodes


  The lymphatic vasculature consists of offering lymphatic vessels, which pierce the capsule and drain into the subcapsular sinus. Lymph continues to drain through the trabecular sinuses to the medullary sinuses and finally exits the hilius via efferent lymphatic vessels.
• Lymphosomes

  Each lymph node drains specific areas of the body and therefore if we only have one enlarged lymph node we want to check if there is something in the draining area tha can justify lymphadenomegaly.

  
• What is indicated to investigate a lymph node?

  Lymph node enlargement (isolated or generalised).

  Suspect of an underlying infectious disease (e.g. Leishmania, FIP, fungi).

  Stage malignant neoplastic diseases.

  Provide material for molecular testing.

  The lymph node is a heterogenous tissue and multiple areas within the node should be sampled to be certain that what has been obtained is representative.
• What does a normal lymph node look like?

  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, neutrophils -> rare.

  
• What are the 4 causes of lymphadenopathy?

  Reactive hyperplasia

  Lymphoma

  Lymphadenitis

  Metastatic neoplasia
• What causes reactive hypoplasia?

  Localised or systemic

  Antigenic stimulation

  • Infectious causes
  • Immune-mediated disease
  • Neoplasia
  • Vaccination.
• Cytology of reactive hyperplasia

  Cytologically can be indistiguishable from a normal lymph node.

  Heterogenous cell population.

  Small lymphocytes are predominant.

  May see increases in intermediate and large lymphocytes (up to 15-20%).

  May see increased numbers of plasma cells (up to 5-10%).

  Occasioanly macrophages (~2%).

  Very few neutrophils, eosinophils, mast cells.
• What is lymphadenitis?

  Accumulation of inflammatory cells.

  Neutrophils (neutrophilic lymphadenitis) - bacterial, immune-mediated, neoplastic.

  Eosinophils (eosinophilic lymphadenitis) - hypersensitivity reaction, parasites, idiopathic, Paraneoplastic (e.g. mast cell tumour, lymphomas).

  Macrophages (macrophagic/ granulomatous lymphadenitis) - chronic inflammatory conditions (e.g. fungal infection, mycobacteriosis, leishmaniasis, FIP).

  Granulomatous and pyogranulomatous are more histological terms.
• Cytology of lymphadenitis

  Similar rot reactive hyperplasia but:

  • >5% neutrophils - Neutrophilic
  • >3% eosinophils - Eosinophilic
  • >3% macrophages - macrophagic

  
• What is lymphoma?

  Neoplasia of lymphocytes in solid tissue.

  Heterogenous disease, several subtypes;

  • Anatomic site (e.g. multi centric, GI, cutaneous)
  • Location of neoplastic cells within the lymph node (e.g. diffuse, follicular, T-zone)
  • Cell morphology (small, large, granular).
  • Cell type (T-cell, B-cell, NK).
  • Biological behaviour (indolent, aggressive).

  The sub-type is related to prognosis and treatment.
• Histopathology/ cytology of lymphoma

  Cytology can be used for diagnosis and staging.

  Accuracy of cytology decreases when we attempt to apply the WHO classification.

  Screening test for prediction of the grade and phenotype.

  Histology is invasive, time consuming and more expensive.

  Cytology combined with ancillary tests (e.g. flow cytometry, immunocytochemistry, PARR) -> acceptable compromise in practice.

  
• Cytology of metastatic neoplasia

  Lumph node 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).

  
• Structure of the spleen

  Capsule - rich in elastic fibres and smooth muscle.

  Red pulp - reservoir of blood.

  White pulp - splenic lymphoid tissue, (antigen presenting cells, macrophages, B and T lymphocytes).

  
• What is the function of the spleen?

  Capsule - contraction can release blood into the circulation (e.g. in response to acute blood loss).

  Red pulp - reservoir of blood, filter for senescent or damages erythrocytes, iron metabolism.

  White pulp - immunity against blood born antigens.
• What is a haematoma?

  Accumulation of blood.

  Haemoglobin breakdown products (haemosiderin - blue, Haematoidin - yellow and rhomboid.

  
• What is the structure of the thymus?

  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
  • Lymphocytes