Pathology of the lymphoid system

Question 1

When is it indicated to investigate a lymph node?

Answer 1

• 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

Question 2

What are the 4 causes of lymphadenopathy?

Answer 2

• reactive hyperplasia
• lymphoma
• metastatic neoplasia
• lymphadenitis

Question 3

What causes reactive hyperplasia? How is it recognisable on cytology?

Answer 3

• antigenic stimulation
  ◦ infectious causes
  ◦ immune-mediated disease
  ◦ neoplasia
  ◦ vaccination
• cytology
  ◦ cytologically can be indistinguishable from a normal lymph node
  ◦ heterogeneous cell population
  ◦ small lymphocytes are predominant
  ◦ may see increase in intermediate and large lymphocytes (up to 15-20%)
  ◦ may see increased numbers of plasma cells (up to 5-10%)
  ◦ occasional macrophages (~ 2%)
  ◦ very few neutrophils, eosinophils, mast cells

Question 4

What 3 cell types can lead lymphadenitis depending on cause?

Answer 4

• neutrophils (neutrophilic lymphadenitis) → bacterial, immune-mediated, neoplastic
• eosinophils (eosinophilic lymphadenitis) → hypersensitivity reaction, parasites, idiopathic, paraneoplastic (e.g., mast cell tumour, lymphoma)
• macrophages (macrophagic/granulomatous lymphadenitis) or neutrophils + macrophages (pyogranulomatous) → chronic inflammatory conditions (e.g., fungal infection, mycobacteriosis, leishmaniasis, FIP)

Question 5

What is lymphoma? What are the different subtypes? How are they distinguishable? How is it staged? How does it appear on cytology?

Answer 5

• neoplasia of lymphocytes in solid tissues
• heterogeneous disease, several subtypes:
  ◦ 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)
• need immunohistochemistry to distinguish
• cytology
  ◦ homogenous appearance
  ◦ most commonly increased percentage (>50%) of large immature lymphocytes
  ◦ may see more mitoses than reactive
  ◦ frequent lymphoglandular bodies (cell fragility - not pathognomonic)
  ◦ tingible bodies macrophages

Question 6

How can we recognise metastatic neoplasia on cytology?

Answer 6

◦ lymph 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)

Question 7

When is it indicated to investigate the spleen?

Answer 7

• diffuse or symmetrical enlargement
• nodular or focal lesions
• abnormal ultrasound appearance
• evaluation of haematopoiesis
• diagnosing neoplasia
• tumour staging
• Often incidental finding

Question 8

What is a normal spleen appearance on cytology?

Answer 8

• similar to normal lymph node but typically more blood
• neutrophils in blood proportions
• ~ 90% small lymphocytes (1-1.5 x RBC)
• medium (2-2.5 x RBC) and large (>3 x RBC) → < 5-10%
• rare plasma cells, macrophages, mast cells

Question 9

What are the 5 types of splenomegaly?

Answer 9

• reactive hyperplasia
• lymphoma
• splenitis
• metastatic neoplasia
• extramedullary hematopoeisis

Question 10

What are possible clinicopathological findings with each of these causes:
- infection/inflammation
- extramedullary hematopoeisis
- haemolymphatic neoplasia
- other neoplasia
- circulatory disturbances

Answer 10

Question 11

What are the 2 main pathologic conditions of the thymus?

Answer 11

• thymoma
• lymphoma

Question 12

Why is it important to distinguish thymoma from lymphoma? How are they diagnosed?

Answer 12

Different origin
Thymoma → epithelial cells
Lymphoma → lymphocytes

Different treatment
Thymoma → surgical treatment
Lymphoma → chemotherapy

Different origin
Thymoma → epithelial cells
Lymphoma → lymphocytes

Different treatment
Thymoma → surgical treatment
Lymphoma → chemotherapy

How do I diagnose?
* Imaging → mass in the cranial mediastinum
* Cytology +/- flow cytometry
* Definitive diagnosis: histopathology
* Paraneoplastic syndrome: hypercalcaemia, myasthenia gravis

Thymoma - cytology
* Epithelial cells
* Small lymphocytes
* Occasional mast cells

Lymphoma - cytology
Homogeneous population of large atypical lymphocytes