1. Related Terms about body defense mechanisms
 Immune system
 Lymphoid system
 Lymphoreticular system
 Reticuloendothelial system (RES)
 Mononuclear phagocyte system (MPS)

2. A complex system of cellular and molecular
components with functions including :
-distinguishing self from not self
-defense against foreign organism for substances
Cellular components: lymphocytes and
macrophages
Molecular components: antibodies and
lymphokines
Immune System
Definition

3. A group of cells having the ability to take up and
sequester inert particles and vital dyes:
-Macrophages or macrophage precursors
-Specialized endothelial cells lining sinusoids of
the liver
-Spleen
-Bone marrow
-Reticular cells of lymphatic system
Reticuloendothelial System (RES)
Mononuclear phagocyte system (MPS)
or Macrophage system
Definition

4. Pathology of thePathology of the
Definitions
Lymphoreticular System
Lymphoreticular System
The system consisting of tissues of the lymphoid and
tissues of the reticuloendothelial system

5. Pathology of thePathology of the
Lymphoid systemLymphoid system
The lymphoid tissues in the body:
Primary (central) lymphoid tissues i.e. thymus and
bone marrow where lymphocytes differentiate from
Secondary (peripheral) lymphoid tissues including
lymph nodes, spleen, and gut (mucosal)-associated
lymphoid tissues (MALT)
Definitions
Lymphoreticular System
Lymphoid system

6. Scope of the Subject
Organs:
• Lymph nodes
• Spleen
• Thymus
• Bone marrow
Disease categories:
• Developmenal disorders
• Traumatic
• Vascular (circulatory
disorders)
• Inflammatory disorders
• Neoplasms and tumor-
like conditions

7. Anatomy of a lymph node

8. Methods for acquiring tissues
 Fine needle aspiration cytology
 Biopsy :
Needle biopsy (core biopsy)
Incisional biopsy (part of node)
Excisional biopsy (whole node)
Lymph node evaluation
 Proper examination of a lymph node is a
complicated task that may require a variety of
specialized procedures depending on the
nature of the CASE

9. Fine needle aspiration (biopsy) cytology
FNA
Definition:
• Fine needle = 22 gauge or smaller
• Useful for :
• Reactive conditions e.g. infectious disease
• Metastatic tumors
• High grade lymphomas

10. ode aspiration, Pap stain: -Adenocarcinoma, metastati

11. Lymph node biopsy
• Core needle biopsy is adequate for the
diagnosis of metastatic carcinoma , but for
primary lymphoid disorders so far not
recommended
• Incisional biopsy is also not preferable in
primary lymphoid disorders
• Exicional biopsy of (whole) node with intact
capsule by sharp dissection is highly useful
for demonstration of nodal architecture,
therefore most favorable

12. Lymph node biopsy
Methods used for evaluation
• Histology / cytology
• Microbiologic (Bacteriologic) study
• Immunohistochemistry
• Cytogenetics and molecular
genetics
• Electron microscopy

13. Reactive changes in lymph node, morphologic features
• Follicular hyperplasia:
• Caused by stimulation that activate humoral immunity
• Increased and enlargement of large B cell rich germinal centres
(secondary follicles) covered by a layer of resting B cell (the mantle zone)
• Follicular center cells comprising the large proliferating lymphocytes
(centroblasts), smaller cells having cleaved nuclear contour (so-called
cleaved cells or centrocytes) and phagocytic macrophages (cells with pale
staining cytoplasm and tingible bodies), some T cells and others
• Paracortical (lymphoid) hyperplasia:
• Caused by stimulation of cellular immunity
• Widening of T cell regions of the node
• Paracortical or interfollicular areas containing activated T cells
(immunoblasts) and others
• Sinus histiocytosis or Reticular hyperplasia:
• Histiocytes = tissue cells, in this meaning includes macrophages and
dendritic cells (Langerhans cells) along the sinusoids

16. tingible body

17. T cell areas) hyperplasia associated with proliferation

18. •histiocytes

19. •Cleaved cell lympho

22. Necrotizing lymphadenitis

24. Histoplasmosis

26. n in viral infection sometime having features mimickin

27. Malignant proliferative diseases of leucocytes
categorization
• Lymphoid neoplasms: being a diverse group of
entities with there phenotypes closely resemble to
particular stage of normal lymphocyte differentiation,
a feature used for diagnosis and classification
• Myeloid neoplasms: arising from hematopoietic stem
cells (that give rise to erythroid, myeloid and
thrombocytic lineages) and leading to peripheral
blood count implying the term leukemia
• Histiocytoses: meaning proliferative lesions of
macrophages and dendritic cells, including entities of
malignant histiocytoses, Langerhans cell
histiocytoses

28. Lymphoma VS Leukemia
• Lymphoma is used to describe proliferation arising
as discrete tissue masses, mainly in lymph nodes
and occasionally in extra-nodal organs / tissues
• Leukemia is used to for neoplastic proliferation of
neoplasms presenting with widespread involvement
of the bone marrow and usually accompanied by
the presence of tumor cells in peripheral blood
Definition: Lymphoma = Any neoplasm of lymphoid tissue
Leukemia = Neoplastic/progressive proliferation of cells in
hematopoietic tissues
At time of clinical presentation

29. Lymphoma (malignant lymphoma)
• Hodgkin Lymphoma (HL) or Hodgkin Disease (HD)
: almost all cases arise in a single node / chain of nodes of
neck region then spreading to contiguous nodes and regions
with rather predictable fashion
: presence of neoplastic cells called Reed-Sternberg cells
among background of reactive cells
• Non-Hodgkin Lymphoma (NHL)
: about 2/3 of cases arising in nodes and the rest in other
tissues/organs (extranodal) with sometimes unpredictable
systemic spreading
: tumor cells = lymphocytes (T-cell, B-cell, & NK-cell)
Definition: Any neoplasm (all as malignant) of lymphoid tissue

31. Case of Hodgkin lymphoma in present textbook
Section of tissue preserved by Dr.Hodgkin

32. Hodgkin Disease = Hodgkin Lymphoma
 Reed-Sternberg cells (R-S cells) are found that in most
cases of HL, derived from B cell, so HL now considered as
unusual B-cell neoplasm
 R-S cells are aneuploidae
 EBV episomes are found in R-S cells, an evidence that
EBV infection involve in the disease formation
 Background cells (reactive cells) accumulation occur as
response to cytokines secreted by the R-S cells
Definition:
-A group of lymphoid malignancy having morphological characteristic as
presence of Reed-Sternberg cells among reactive lymphocytes, histiocytes and
granulocytes.
- Arises in single node or chain of nodes with predictable pattern of spreading.

33. a of lymph node showing Reed-Sternberg cells among

34. A Reed-Sternberg
cell showing
owl’s eyes
features with larg
e
inclusion-like
nucleoli among
background cells

35. R-S cell: now considered as tumor cell in HD that elaborates
substances causing mixed cellularity in the lesion
D30 positive reaction of R-S cell

36. Hodgkin lymphoma, mixed cellular

37. Nodular sclerosis Hodgkin lymphoma

38. gkin lymphoma, lymphocyte-rich with pop-corn R-S c

39. •R-S cell variants •Mummified cell

43. Classification of Hodgkin Lymphoma, WHO
• Nodular sclerosis
• Mixed cellularity
• Lymphocyte-rich
• Lymphocytic depletion
• Lymphocytic predominance

44. Some important principles in lymphoid neoplasms
particularly NHL
• Monoclonal :-each developing lymphocyte has a single/unique
antigen receptor, therefore the daughter cells derived from malignant
progenitor share the same antigen receptor gene, e.g. production of the
same immunoglobulin resulting in monoclonal gammopathy in myeloma
• Neoplastic B and T cells tend to behave like their
normal (original) cells, leading to characteristic pattern of
involvement, e.g. follicular lymphoma, mantle cell lymphoma
• Recirculation of lymphoid cells (both the normal and
the neoplastic) through the lymphatics and peripheral
blood: dissemination of NHL always considered since the time of
diagnosis
• Majority of lymphoid neoplasm are of B cell origin
• Disruption of the normal architecture and function of
immune system: evident as susceptibility to infection and
manifestation of autoimmunitity in some cases

45. Aetiological Factors in Lymphomas
• Genetic factors:
– Inherited genetic factors
– Chromosomal aberrations e.g. translocations
– Oncogenes
• Infections:
– Viruses: Epstein-Barr virus (EBV) and Burkitt lymphoma
Kaposi Sarcoma herpesvirus (KSHV) and B-cell lyphoma
HTLV-1 and adult T-cell leukemia/lymphoma
– Helicobacter infection: gastric B-cell lymphoma
• Environments: contamination of radioactive substances from
nuclear power plants and nuclear weapons
• Iatrogenic factors: radiotherapy and certain kind of
chemotherapeutic agents

46. Clinical manifestations of lymphomas

47. Manifestations of Lymphomas

48. Lymphoma, small bowel extra-nodal manifestation
•Monotonus growth of neoplastic lymphocytes

49. features of lymph node
lymphoma
oscopic features in H&E stain
notonus growth pattern

50. Follicular lymphoma in microscopic sec
oss features of follicular NHL
cut section

51. Tumor cells in the follicular structu

52. Neoplastic follicleymphoid follicles with the mantle zone

53. •Small cell •Large cell •Anaplastic / blast c

54. Diffuse lymphoma

55. itt lymphoma: section showing starry sky feature

57. Non-Hodgkin Lymphoma classification
• Rappaport’s classification
• WHO classification
• Working (international) formulation classification
• Revised European-American Classification of
Lymphoid Neoplasms (REAL)
Controversy and Confusion in classification of NHL and related
lymphoid neoplasms are long-time well known for learners in
pathology

62. Categorization based on morphologic features
• Diffuse lymphoma
– Small cell
– Mixed small and large cell
– Large cell
– Lymphoblastic
• Follicular lymphoma
– Small cell
– Mixed small and large cell
– Large cell
• Burkitt lymphoma
• Anaplastic large cell lymphoma

63. Classification of lymphoid malignancy
based on cell origin
• Precursor B-cell neoplasms =neoplasms of immature B cells
• Peripheral B-cell neoplasms = neoplasms of mature B cells
• Precursor T-cell neoplasms =neoplasms of immature T cells
• Peripheral T-cell and NK-cell neoplasms = neoplasms of
mature T cells and natural killer cells
• Hodgkin lymphoma =neoplasm of Reed-Sternberg cells and
variants (now believed as transformed B cells in most
cases)

69. Hairy Cell Leukemia

70. Burkitt’s lymphoma

79. Treatment of Lymphomas
• Surgery: Not as definite treatment for disease but
resection of the hollow organ with transmural
involvement insisted to prevent perforation
• Radiation therapy: in a large mass lesion and for
some specific type particularly HL
• Chemotherapy: with multiple drugs
• Immunotherapy
• Bone marrow transplantation
• Multimodality
By a long-time-development in treatments, several types
of lymphomas can now be well controlled and/or cured.

80. Lymphoma in immunodeficiency states
• Primary immunodeficiency
• Organ transplant recipients
• Patients with HIV infection
• Other acquired disease of immunosystem, e.g. rheumatoid
arthritis, Sjogren syndrome, Hashimoto thyroiditis etc.

81. Langerhans cell histiocytosis
Langerhans cell histiocytosis presents as three
clinicopathologic entities:
1.Multifocal multisystem Langerhans cell histiocytosis
(Letterer-Siwe disease)
2.Multifocal unisystem Langerhans cell histiocytosis
(Hand-Schuller-Christian disease)
3.Eosinophilic granuloma: usually unifocal lesion involving
bone, but sometimes multifocal and involvement in other
organs
Definition: Proliferative disorders of dendritic cells, the
Langerhans cells or antigen presenting cells (APC)

82. Eosinophilic granuloma

83. Eosinophils
Langerhans cells

84. so-called Malignant Histiocytosis
- Rappaport, 1966: proposed the term malignant histiocytosis for
disease systemic neoplastic proliferation of cells histologically
identified as histiocytes with fever and fatal outcome.
- Scott & Robb-Smith, 1939: described the same entity as
Histiocytic Medullary Reticulosis (HMR).
- Several cases found as virus-associated hemophagocytic
syndrome, having the same clinico-pathologic features.
- Familial hemophagocytic reticulosis, also found as viral
infection in a family with immune defect.
- Cell marker and molecular analysis studies showins most
cases as high grade NHL, usually anaplastic large cell (Ki-1).

85. End of the Session