Pathology of the Lymphoid System

primary lymphoid organs

-thymus

-bone marrow

-bursa of fabricius

secondary lymphoid organs

-spleen

-LN

-lymph nodules (MALT, GALT)

lymphoid system is…

-interconnected

-lymphocytes continually recirculate

-connected to the blood circ via the thoracic duct

high endothelial venules

specialised cuboidal endothelial cells that facilitate receptor mediated transmigration of lymphocytes from blood

spleen lymphatic drainage

none

lymph node structure

-multiple afferent lymphatic vessels drain into subscapular sinus into trabecular sinuses into medullary sinuses and out into efferent lymphatic vessels

how do lymphocytes enter LN

-most through HEVs

-some through lymphatic circulation

lymphosomes

can look at where closer lymph node is to lump to see if lymph affected

the region of skin that is drained by the ln

can go back to the area from the enlarged ln to see if problem is there

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

when indicated to investigate LN

-LN enlargement

-suspect underlying infectious disease e.g. leishmania, FIP, fungi

-stage malignant neoplastic disease

-provide material for molecular testing

label pic

-left is normal

-middle is hyperplastic

-right is hyperplastic only on one side so shows importance of sampling all over LN

• ln gets lymphatic material from diff afferent lymphatic vessels so cna be compartmentalised

how to FNA LN well

-avoid aspiration of centre of markedly enlarged LN→ often necrotic

-spread gently→ lymphocytes are fragile

-non suction to minimise blood contam

-keep cytologic prep away from formalin fumes

-ideally take sample before giving steroids (sus lymphoma)

what is this sample

perinodal fat

• can be accidentally sampled

what is this sample

slaivary gland

-epithelial cells

-cells in rows which is due to proteinaceous viscous saliva (windrowing)

-can also be accidentally sampled

normal LN look like

-small lymphocytes mostly

-medium and large less than 5-10%

-plasma cells, macrophages, mast cells, neutrophils are rare

-lymphoglandular bodies- fragile, fragments of cytoplasm

compare lymphocyte to rbc size

4 causes of lymphadenopathy

-reactive hyperplasia

-lymphoma

-lymphadenitis

-metastatic neoplasia

reactive hyperplasia spread

localised or systemic

stimulation of reactive hyperplasia

antigenic→ stimulate the LN to produce lymphocytes

-infectious

-immune mediated

-neoplasia

-vaccination

cytology of reactive hyperplasia

-indistinguishable from normal

-heterogenous cells

-small lymphocytes predominantly

-may see increase in intermediae and large

-may see more plasma cells

-cc macrophage

-few neutrophils, eosinophils, mast cells

plasma cell on cytology

has a vacuole where golgi body is as produce antibodies from here

lymphadenitis

-accumulation of inflam cells

neutrophilic lymphadenitis cause

-bacterial

-immune mediated

-neoplastic

eosinophilic lymphadenitis causes

-hypersensitivity reaction

-parasites

-idiopathic

-paraneoplastic (e.g. mct, lymphoma)

macrophagic/granulomatous lymphadenitis or pyogranulomatous causes

-chronic inflam conditions e.g. fungal infection, mycobacteriosis, leishmaniasis, FIP

lymphadenitis on histology

-more than 5% neutrophils then neutrophilic

-more than 3% eosinophils then eosinophilic

-more than 3% macrophages then macrophagic

how does mycobacteria appear on stain

do not stain, rods

lymphoma

-neoplasia of lymphocytes in solid tissues

subtypes of lymphoma

anatomic site (e.g., multicentric, 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)

prognosis for lymphoma

b better than t (terirble)

lymphoma subtype classification

based on histopathology and immunohistochemistry

Subtype related to prognosis and treatment

immunohistochemistry

apply antibodies to detect antigen on surface of cells

• differentiate t or b

lymphoma cytology

-diagnosis and staging

-accuracy decreases when attempt to apply WHO classification

-screening test for prediction of grade and phenotype

-not good for further classifying→ need histology

lymphoma histology

-invasive, time consuming, more expensive

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

approach to lymphadenopathy

how lymphoma looks on cytology

-homogenous (normally hetero)

-increased large immature lymphocytes

-may see more mitoses than reactive

-frequent lymphoglandular bodies

-tingible (stained) body macrophages

tingible body macrophage

phagocytosed debris of lymphocytes in macrophages

metastatic neoplasia

-lymph node maybe reactive

-presence of cells not normally in LN

-increased number of cells normally present often with atypical morphology

metastatic carcinoma

metastatic melanoma→ dark black brown pigment

approach to LN cytology

structure of spleen

-capsule

-red pulp

-white pulp

capsule of spleen

rich in elastic fibres and smooth muscle

red pulp of spleen

splenic sinusoids (rich in blood)

white pulp of spleen

splenic lymphoid tissue (antigen presenting cells, macrophages, b and t lymphocytes)

capsule of spleen function

contraction can release blood into circ (e.g. in response to acute blood loss)

red pulp of spleen function

reservoir of blood, filter for senescent or damaged erythrocytes, iron metabolism

white pulp of spleen function

immunity against bloodborne antigens (antigenic sensitisation)

when indicated to investigate spleen

-diffuse or symmetrical enlargement

-nodular or focal lesions

-abnormal US appearance

-evaluation of haematopoiesis

-diagnose neoplasia

-tumour staging

-often incidental

what is spleen good indication for

bone marrow→ easier to sample spleen than bm

key points for sampling spleen

-non suction technique to min blood contam

-spread gently

-keep cytologic prep away from formalin fumes

-avoid contam with lubricant gel→ bc usually US guided

• use water/ saline

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-ideally take sample before giving steroids

normal spleen look

-similar to LN but more blood

-neutrophils in blood

-90% small lymphocytes

-medium and large less than 5-10%

-rare plasma cells, macrophages, mast cells

splenomegaly causes

-reactive hyperplasia

-lymphoma

-splenitis

-metastatic neoplasia

-extramedullary haematopoieis

extramedullary haematopoiesis

if bone marrow having problems then spleen makes precursors (like in foetal life)

can see fe on splenic samples

erythroid island

erythrocyte precursors around macrophage to get iron to make haemoglobin

megakaryocyte

large platelet precursor cell found in the bone marrow or made in spleen when bone marrow not operating

infection or inflam of the spleen enlargement

-symmetrical or nodular enlargemenet

infection or inflam of spleen clinicopathological findings

-inflam leucogram

-hyperglobulinaemia

-infectious agent (e.g. leishmania, toxoplasma)

extramedullary haematopoiesis enlargement of spleen

symmetrical or nodular

extramedullary haematopoiesis clinicopathological findings

-anaemia

-other cytopaenias seen on CBC

haemolymphatic neoplasia type of enlargement

symmetrical or nodular

haemolymphatic neoplasia (e.g. lymphoma, multiple myeloma) clinicopathological findings

-lymphocytosis

-atypical cells in circulation

-cytopenias seen on CBC

-hyperglobulinaemia

-monoclonal gammopathy

-paraproteinuria

neoplasia like hystiocytic sarcoma or haemangiosarcoma enlargement

symmetrical or nodular

neoplasia like hystiocytic sarcoma or haemangiosarcoma clinicopathological findings

-regen anaemia +/- other cytopenias

-schistocytes

-acanthocytes

-thrombocytopenia

circulatory disturbances e.g. haematoma, torsion, splenic congestion enlargement

symmetrical or nodular

circulatory disturbances e.g. haematoma, torsion, splenic congestion clinicopathological findings

-regen anaemia

-abnormal liver values

-inflam/stress leucogram

infectious agents of spleen

-leishmania

-toxoplasma

neoplasia of spleen

-multiple myeloma

-haemangiosarcoma (mesenchymal)

multiple myeloma

tumour of plasma cells

melanoma

mast cell tumour

carcinoma

haematoma

-blood

-haemoglobin breakdown products (haemosiderin is blue, haematoidin is yellow and rhomboid)→ chronic haemorrhage

approach to spleen cytology and disease

structure of thymus

-primary lymphoid organ for development of t lymphocytes

where is thymus located

cranial mediastinum

-prominent before puberty then replaced by adipose tissue

2 most important components of thymus

epithelial cells and lymphocytes (CD4+ CD8+)

two pathologies of thymus

-thymoma

-lymphoma

thymoma origin

epithelial cells

lymphoma origin

lymphocytes

how do we differentiate between lymphoma and thymoma

differentiate between the cells

Thymoma → epithelial cells

Lymphoma → lymphocytes

treatment of thymoma

surgical

treatment of lymphoma

chemotherapy

how to investigate/ differentiate between thymoma and lymphoma

-imaging mass in cranial mediastinum

-cytology or/and flow cytometry

-histopathology for definitive

-paraneoplastic syndromes like hypercalcaemia, myasthenia gravis

what is myasthenia gravis most common in

thymoma

thymoma cytology

-epithelial cells

-small lymphocytes

-occasional mast cells

lymphoma cytology

-homogenous population of large atypical lymphocytes