Ap 50 10-15 1 re system

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Ap 50 10-15 1 re system

  1. 1. Related Terms about body defense mechanisms  Immune system  Lymphoid system  Lymphoreticular system  Reticuloendothelial system (RES)  Mononuclear phagocyte system (MPS)
  2. 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. 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. 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. 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. 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. 7. Anatomy of a lymph node
  8. 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. 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. 10. ode aspiration, Pap stain: -Adenocarcinoma, metastati
  11. 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. 12. Lymph node biopsy Methods used for evaluation • Histology / cytology • Microbiologic (Bacteriologic) study • Immunohistochemistry • Cytogenetics and molecular genetics • Electron microscopy
  13. 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
  14. 14. tingible body
  15. 15. T cell areas) hyperplasia associated with proliferation
  16. 16. •histiocytes
  17. 17. •Cleaved cell lympho
  18. 18. Necrotizing lymphadenitis
  19. 19. Histoplasmosis
  20. 20. n in viral infection sometime having features mimickin
  21. 21. 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
  22. 22. 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
  23. 23. 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
  24. 24. Case of Hodgkin lymphoma in present textbook Section of tissue preserved by Dr.Hodgkin
  25. 25. 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.
  26. 26. a of lymph node showing Reed-Sternberg cells among
  27. 27. A Reed-Sternberg cell showing owl’s eyes features with larg e inclusion-like nucleoli among background cells
  28. 28. 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
  29. 29. Hodgkin lymphoma, mixed cellular
  30. 30. Nodular sclerosis Hodgkin lymphoma
  31. 31. gkin lymphoma, lymphocyte-rich with pop-corn R-S c
  32. 32. •R-S cell variants •Mummified cell
  33. 33. Classification of Hodgkin Lymphoma, WHO • Nodular sclerosis • Mixed cellularity • Lymphocyte-rich • Lymphocytic depletion • Lymphocytic predominance
  34. 34. 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
  35. 35. 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
  36. 36. Clinical manifestations of lymphomas
  37. 37. Manifestations of Lymphomas
  38. 38. Lymphoma, small bowel extra-nodal manifestation •Monotonus growth of neoplastic lymphocytes
  39. 39. features of lymph node lymphoma oscopic features in H&E stain notonus growth pattern
  40. 40. Follicular lymphoma in microscopic sec oss features of follicular NHL cut section
  41. 41. Tumor cells in the follicular structu
  42. 42. Neoplastic follicleymphoid follicles with the mantle zone
  43. 43. •Small cell •Large cell •Anaplastic / blast c
  44. 44. Diffuse lymphoma
  45. 45. itt lymphoma: section showing starry sky feature
  46. 46. 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
  47. 47. 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
  48. 48. 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)
  49. 49. Hairy Cell Leukemia
  50. 50. Burkitt’s lymphoma
  51. 51. 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.
  52. 52. 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.
  53. 53. 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)
  54. 54. Eosinophilic granuloma
  55. 55. Eosinophils Langerhans cells
  56. 56. 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).
  57. 57. End of the Session

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