1. Haematological Neoplasia:
Leukemias - Acute & Chronic
Lymphomas - Hodgkins & Non-Hodgkins (T cell, B cell, histiocytic & others)
Premalignant Conditions:
Myeloproliferative syndromes (MPS)
Myelodysplastic syndromes (MDS)

2. Lymphomas

3. Introduction: Neoplastic lymphoid proliferation
Two types – Hodgkins & Non-Hodgkins.
Fever, lymphadenopathy,
Immunodeficiency / autoimmune syndrome
Viral, genetic, unknown etiology.
Lack of programmed cell death - Apoptosis

4. Lymphoma’s Where They Begin
Lymphomas are a cancer of the lymphatic system
Lymphatic vessels
Lymph nodes (underarms, groin, neck, spleen, tonsils and bone marrow)

5. Lymphoma’s Where They Begin
The Lymphatic system is our bodies main fight against infection
Lymphocytes (B-cell and T-cell)
Carried through our lymphatic system and help our bodies fight infection
Lymphocytes are carried through the lymph vessels as well as the blood stream, so cancer can start in nodes and spread anywhere throughout the body.

6. Lymphatic System

7. Lymphoma
Row of enlarged lymph nodes

8. Lymphoma - Gross

9. Lymphoma Intestine

10. Lymphoma Intestine

11. Mediastinal Lymphnodes-NHL

12. Hodgkins Lymphoma (HL)

13. Hodgkin’s Disease
Is a malignant lymphoma characterized by the presence of atypical, multinucleated giant cell (Reed-Sternberg cell)
The disease is slightly more common in men
Most patients have asymptomatic lymphadenopathy at the time of diagnosis
The initial site of nodal involvement is:
Cervical (65-80%)
Axillary (10-15%)
Inguinal (6-12%)

14. Reed-Sternberg Cell

15. Hodgkins lymphoma

16. Hodgkins lymphoma cells

17. Hodgkins Lymphoma

18. Causes/Risk Factors The exact cause of Hodgkin’s disease is unknown.
Also, a virus called Epstein-Barr may be involved with an increased risk of Hodgkin’s.
Also, Agent Orange, used during the Vietnam War is linked with the development of Hodgkin’s.
Siblings of a Hodgkin’s victim are more at risk for developing the disease.
It is more common for men to have the disease.
Hodgkin’s occurs most often in those between 15 and 34 or over the age of 55.

19. Classification of Hodgkin’s Disease
Treatment depends on
The anatomic distribution of the disease and the presence or absence of specific symptoms
The stage of the disease
The histopathologic subtype

20. Classification of Hodgkin’s Disease
The Rye classification
Based on four histopathologic subtypes
Lymphocytes predominance
Nodular sclerosis
Mixed cellularity
Lymphocytes depletion

21. Classification of Hodgkin’s Disease
Histopathologic diagnosis
Is made by lymph node biopsy
Nodes from the lower cervical or axillary areas provide the best tissue for evaluation
Ann Arbor staging classification
A classification based on anatomic distribution of the disease
Stage I disease – Stage IV disease

23. Splenic Involvement
The probability of splenic involvement increases with increasing spleen size
The absence of splenomegaly does not exclude splenic involvement
Upon gross examination of the spleen a grayish white nodule ranging from several millimeters to several centimeters is apparent with Hodgkin’s disease
Liver involvement with Hodgkin’s disease rarely occurs in the absence of splenic disease

24. Classifications Classic Hodgkin’s divisions Nodular Sclerosing
Mixed Cellularity
Lymphocyte rich
Lymphocyte depleted

25. Nodular Sclerosing >60% of cases Connective tissue RS cells
Lacunar cells
other cells

26. Mixed Cellularity 15 – 30% cases Mixed cells Lymphocytes Histocytes
Eosinophils
Plasma cells
RS cells
Variants
+Necrosis

27. Lymphocyte rich <5% cases Large numbers of Lymphocytes
May suppress other cells
RS cells
Not to be confused with LP Hodgkin’s

28. Lymphocyte depleted
<1% cases
Lymphocytes rare
RS cells predominate

29. Symptoms & Presentation
Swollen, painful lymph nodes
Fatigue, etc.
Generalized iching
Appetite, weight loss
Neck %/or back pain
Hair loss
Night sweats

30. Hodgkin’s Disease
Symptoms such as fever, night sweats, weight loss and pruritus are indicative of widespread involvement and are unfavorable prognostic signs
A typical fever pattern is a high-temperature alternating for a few days with an afebrile period
Many patients have a mild normochromic, normocytic anemia
1/3 have a leukocytosis due to a neutrophil increase
Eosinophilia is frequently present

31. Prognosis Staging Nodular or Diffuse Anatomical Staging
Stage I- one region
Stage II- two regions, same side diaphragm
Stage III- two regions, both sides of diaph
Stage IV- spread outside of lymph system
I & II- >10 years
III & IV - < 6 years

32. Current Treatment of Hodgkin’s Disease
Integrates radiation therapy and combination chemotherapy to achieve the maximum potential for cure
Untreated Hodgkin’s has a five-year survival rate of 5%
The Stanford experience-patients at all stages have survival rate of 86%
Patients in stage IV have a generally poor prognosis

33. Non-Hodgkins Lymphoma (NHL)

34. NON- Hodgkin’s Lymphoma
Absence of Reed-Sternberg Cells
May result from damage to DNA that controls growth of cells in immune system
Increased incidence in immunodeficiency

35. Associated with Non-H lymphoma
SLE
Celiac Disease
AIDS
Organ transplant patients
Rheumatoid Arthritis

36. Causes and Risk Factors
The Exact causes are still unknown
Higher risk for individuals who:
Exposed to chemicals such as pesticides or solvents
Infected w/ Epstein-Barr Virus
Family history of NHL (although no hereditary pattern has been established)
Infected w/ Human Immunodeficiency Virus (HIV)

37. Classifications Based on cell type and location(s)
Non symptomatic ->
Aggressive
Worst prognosis < 1 year

38. Non-Hodgkin’s Lymphoma (NHL)
A diverse group of primary malignancies of lymphoreticular tissue
The clinical course and natural history is more variable than Hodgkin’s disease
The pattern of spread is irregular and more patients have leukemic features
Current histologic classifications utilize electron microscopic morphology, histochemical studies and selected cell surface antigens.
For our purposes NHL is classified according to nodular (favorable) and diffuse (unfavorable) types

39. NHL
In contrast to Hodgkin’s disease, about two-thirds of patients initially have asymptomatic lymphadenopathy
In addition to peripheral and mediastinal lymphadenopathy NHL is commonly found initially as an abdominal mass or as hepatic or splenic enlargement
Fever, weight loss and night sweats are frequently present
The median age at diagnosis is 50
No sex preference is noted

40. NHL
Patients below 35 or over 65 are more likely to have diffuse histology
As with Hodgkin’s, chemotherapy and / or radiation therapy are the primary forms of treatment
Staging laparotomy is seldom required
Significant therapeutic benefit can be achieved by splenectomy in % of patients with advanced lymphomas (including Hodgkin’s disease)

41. Classification
Usually classified by how the cells look under a microscope and how quickly they grow and spread
Aggressive lymphomas (high-grade lymphomas)
Indolent Lymphomas (low-grade lymphomas)

42. Classification of Malignant Lymphomas
Low Grade: small lymphoid cells, nodular growth
Intermediate Grade: large cells, follicular and diffuse patterns
High Grade: immunoblastic, lymphoblastic, Burkitt’s disease
T-cell lymphomas: peripheral, cutaneous

43. Non-Hodgkin’s Lymphoma Staging
Stage is the term used to describe the extent of tumor that has spread through the body( I and II are localized where as III and IV are advanced.
Each stage is then divided into categories A, B, and E
A: No systemic symptoms
B: Systemic Symptoms such as fever, night sweats and weight loss
E: Spreading of disease from lymph node to another organ

44. Staging

45. Non-Hodgkin’s Lymphoma
Two main types of Non-Hodgkin’s Lymphoma:
B-Cell and T-Cell Lymphomas
B-Cell lymphomas (80%)
T-Cell lymphomas (15%)

46. NHL – Classification: According to cell type
T cell, B cell, Histiocytic & Misc. NHL
According to Clinical grade
Low grade, Intermediate & High grade NHL.
Histopathological
Diffuse/Follicular NHL,
Small, Intermediate & Large cell NHL
Ex: Lennert’s lymphoma is a low grade Tcell NHL.
Burkitt’s lymphoma is a high grade B cell NHL

47. Kiel Classification of NHL
B Cell NHL:
Low Grade: lymphocytic, plasmacytic, centrocytic, mixed centrocytic centroblastic.
High Grade: Centroblastic, Immunoblastic, Burkitts, lymphoblastic.
T Cell NHL:
Low Grade: lymphocytic, mycosis, Lennerts
High Grade: immunoblastic, lymphoblastic etc.
Rare types:

48. NCI – Working Formulation
Low-grade NHL:
Small lymphocytic
Follicular small cleaved
Intermediate-grade NHL:
Follicular large cell
Diffuse small cleaved
High-grade NHL:
Immunoblastic
Lymphoblastic
Miscellaneous: Histiocytic, Mycosis etc.

49. Diffuse - & - Follicular
NHL- Histologic types
Diffuse - & - Follicular

50. Small – Intermed. – Large
NHL- Histologic types
Small – Intermed. – Large

51. Staging of Lymphoma

52. Lymphoma spread to Spleen

53. Lymphoma spread to Spleen

54. Laboratory Diagnosis:

55. Laboratory Diagnosis:
Haematological:
Normocytic normochromic anemia, High ESR*
Leucocytosis, Eosinophilia, lymphopenia
Leukoerythroblastic picture - BM infiltration*
Bone marrow:
Normal, or late involvement.
Trephine biopsy- diffuse or follicular infiltration
Biochemical:
High serum LDH – poor prognosis
Hypercalcemia, Alkaline phosphatase, Uric acid.
Serum transaminases & Bilirubin – Liver

56. Laboratory Diagnosis:
Immunological:
Monoclonal gammopathy –B cell NHL, Myeloma
Low normal gammaglobulins
Autoimmune hemolytic anemia – auto ab.
Karyotypic/Genetic:
t(14;18) – B cell follicular (14* heavy chain)
t(11;14) – diffuse NHL

57. Diagnosis X-Rays CT scans Magnetic Resonance Imaging (MRI) Biopsy
Lymphangiogram
Pictures of the lymphatic system taken w/ x-ray after a special dye is injected to illuminate lymph nodes and vessels

58. Treatment
Non-Hodgkin’s Lymphoma is usually treated by a team of physicians including hematologists, medical oncologists and a radiation oncologist.
In some cases such as for Indolent lymphomas, the Doctor may wait to start treatment until the patient starts showing symptoms, known as “watchful waiting”

59. Treatment Options Chemotherapy Radiation Bone Marrow Transplantation
Surgery
Bortezomib (Velcade)
Immunotherapy
Using the bodies own immune system combined with material made in a lab.

60. Treatment: Staging & grading Chemotherapy – CHOP, MCHOP..
Radiotherapy – Local/regional/TBI
Combination –
Intensive Chemo/Radio-TBI
with Autologous bone marrow rescue.

61. Survival Rates Survival Rates vary widely by cell type and staging.
1 Year Survival Rate: 77%
5 Year Survival Rate: 56%
10 Year Survival Rate: 42%

62. Burkitt’s Lymphoma

63. Burkitt’s Lymphoma Unusual, B-Lymphoblastic high grade
Young african children, jaw bones
Isolated histiocytes, starry sky pattern
EBV infection related. t(8;14)
Chemotherapy – good response
But relapse usual, 30% cure.

64. Burkitt’s Lymphoma

65. Burkitt’s Lymphoma L.N.

66. Lymphoma Summary: Solid malignancy of lymphoid tissue.
Lymphadenopathy, fever, anemia.
Hodgkins & Non-Hodgkins (NHL) types.
RS-Cells, eosinophilia – Hodgkins.
Low-grade, Intermediate & High grade.
Blood, Biochemical, BM, LN - biopsy
Immunological & Genetic tests.
Chemotherapy, Radiotherapy, combination