1. LYMPHOMA
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2. LYMPHOMA
Malignant lymphoma is a term given to tumors of the lymphoid system and specifically of lymphocytes and their precursor cells
 The name often refers to just the cancerous ones rather than all such tumors.
Many lymphomas are known to be due to specific genetic mutations.
3rd most common cancer in children with incidence of 15 per million children
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3. Malignant lymphoma
Hodgkin lymphoma
Non Hodgkin lymphoma

4. HODGKIN’S LYMPHOMA
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5. Hodgkin disease Definition:
A neoplastic transformation of lymphocytes particularly in lymph nodes.
Characterized by:
1) the presence of Reed-Sternberg cells on histology
2) spreading in an orderly fashion to contagious lymph nodes
( For example, Hodgkin lymphoma that starts in the cervical lymph nodes may spread first to the supraclavicular nodes then to the axillary nodes )
6% of childhood cancer
5% of cancer in < 14 yr
15% in person yr
Rare < 10 yr

6. Red-Sternberg cells
Large cells ( >45um in diameter) with classically binucleate or bilobed central nucleus each with a large acidophilic central nucleoli surrounded by a clear halo. “owl’s eye appearance”
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7. Epidemiology of Hodgkin’s lymphoma
Hodgkin disease has bimodal age distribution--one peak in the 20s and 60s.
Early peak middle to late 20s
Second peak after 50 yr
Sex Male : Female
4: 1 for 3-7 yr : 1 for 7-9 yr : 1 for > 10 yr
100 folds risk for unaffected monozygotic twin of affected twin
Associated with specific HLA antigen
Infectious agents
Human herpes virus 6
CMV
Epstein – Barr virus
Immunodeficiency
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8. Etiology/Risk Factors
Doctors seldom know why one person develops Hodgkin lymphoma and another does not. But research shows that certain risk factors increase the chance that a person will develop this disease.
Having one or more risk factors does not mean that a person will develop Hodgkin lymphoma. Most people who have risk factors never develop cancer.
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9. Risk Factors 1) Certain viruses: Epstein-Barr virus (EBV)
Human immunodeficiency virus (HIV)
2) Weakened immune system:
inherited condition
certain drugs used after an organ transplant
3) Age:
Hodgkin lymphoma is most common among teens and adults aged 15 to 35 years and adults aged 55 years and older.
4) Family history:
Family members, especially brothers and sisters, of a person with Hodgkin lymphoma or other lymphomas may have an increased chance of developing this disease.
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10. Classification Rye Classification System
Lymphocyte Predominant % of patients More common in male Younger patients Localized disease
Has best prognosis Mixed cellularity 30% of patients < 10 yr of age Advanced disease Extranodal extension
Lymphocyte depletion Rare in children Common with HIV
Has worst prognosis Nodular sclerosis Most common 40% of younger patients 70% of adolescents
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11. REAL Classification ( Revised European – American Classification of Lymphoid Neoplasms )
Nodular lymphocyte predominance
Classical Hodgkin lymphoma
Lymphocyte rich
Mix cellularity
Nodular sclerosis
Lymphocyte depletion
Anaplastic large cell lymphoma Hodgkin like
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12. Clinical presentation
Enlarged, painless, rubbery, non- erythematous, nontender lymph nodes are the hallmark of the disease.
May become painful after drinking alcohol
Hepatosplenomegaly
Cough, dyspnea, hypoxia
Pleural or pericardial effusion
Heptocellular dysfunction
B.M infiltration(Anemia, neutropenia, thrombocytopenia)
25% have ''B'' symptoms
Although pruritus is common in the disease it is not one of the ‘’B’’ symptoms.
Cervical, supraclavicular and axillary lymphadenopathy are the most common initial signs of the disease.
Disease below diaphragm is rare (only3%)
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13. Unexplained fever > 390C Weight loss > 10% in 3m
Systemic Symptoms (B symptoms)
Important in staging
Unexplained fever > 390C
Weight loss > 10% in 3m
Drenching night sweats
Immune System abnormalities
Anergy to delayed-hypersensitivity skin test
Abnormal cellular immune response
Decreased CD4:CD8 ratio
Reduce natural killer cell cytotoxicity
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14. Extralymphatic sites may be involved such as: # Spleen # Liver
# Bone marrow
# Lung
# CNS
Extralymphatic involvement is more common with non-hodgkin lymphoma.
Emergency presentation:
Infections
SVC obstruction ( facial edema, increased JVP and Dyspnea)
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15. Staging of Hodgkin’s Lymphoma
The doctor considers the following to determine the stage of Hodgkin lymphoma:
The number of lymph nodes affected.
Whether these lymph nodes are on one or both sides of the diaphragm.
Whether the disease has spread to the bone marrow, spleen, liver, or lung.
Each stage is divided into A or B symptoms according to the presence of systemic symptoms.
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16. Ann Arbor Staging Classification for Hodgkin Disease
Stage I
Involvement of a single lymph node (1)
or of a single extra lymphatic site or organ(1f)
Stage II
Involvement of two or more lymph node regions on the same side of the diaphragm(II)
or localised involvement of an extra lymphatic site
or organ and one or more lymph node regions on the same side of the diaphragm (IIf)
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17. Stage III Involvement of lymph node regions on both sides of the diaphragm (III) which may be accompanied by the involvement of spleen (IIIS) or by localized involvement of an extra lymphatic site or organ ( IIIf) or both ( IIIsf) Stage IV Diffuse or disseminated involvement of one or more extra lymphatic organs or tissues with or without associated lymph node involvement. The absence or presence of fever > 38C for three consecutive days , drenching night sweats , or unexplained loss of > 10% body weight in the 6 months preceding admission are to be denoted in all cases by the suffice letters A & B respectively.
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19. DIAGNOSIS
An excisional lymph node biopsy is the essential first step in diagnosis.
A biopsy is the only sure way to diagnose Hodgkin lymphoma.
Excisional Biopsy
Light Microscopy
Immunocytochemistry
Molecular Studies
Chest X – Ray
Mediastinal Mass
CT Scan
Chest
Abdomen
Pelvis
Blood CP & ESR
LFT’s
Bone Marrow Aspiration
Serum Copper & Ferritin
Bone Scan
Gallium 67 Scan / FDG/PET
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20. TREATMENT Treatment depends on : Current Treatment Regimen
Stage of the disease
Age at diagnosis
Presence / absence of B symptoms
Presence of hilar lymphadenopathy
Presence of bulky nodal disease
Current Treatment Regimen
Combined chemotherapy with or without low dose involved field radiation therapy
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21. Chemotherapy Regimens
TREATMENT
Chemotherapy Regimens
MOPP
(Mechlorethamine , Vincristine , Procarbazine , Prednisolone)
COPP
(Cyclophosphamide , Vincristine , Procarbazine , Prednisolone)
ABVD
(Adriamycin , Bleomycin , Vinblastine , Dacarbazine)
BEACOPP ( For advanced stage disease )
(Bleomycin , Etoposide , Doxorubicin , Cyclophosphamide , Vincristine , Procarbazine , Prednisolone)
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22. TREATMENT Therapy is entirely based on the stage.
Localized disease ( stage IA and IIA ) is managed predominantly with radiation.
All patients with evidence of ‘’B’’ symptoms as well as stage III and IV are managed with chemotherapy.
The most effective combination chemotherapeutic regimen for Hodgkin lymphoma is ABVD ( adriamycin, bleomycin, vinblastin and dacarbazine).
ABVD is superior to MOP (meclorethamine, vincristin(oncovin) , prednisolone and procarbazine) because ABVD has fewer side effects such as:
1) Permanent sterility
2) Secondary cancer formation
3) Aplastic anemia
4) Peripheral neuropathy
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23. International Prognostic Index
The International Prognostic Index (IPI) was first developed to help doctors determine the prognosis for people with fast-growing lymphomas. The index depends on 5 factors:
1) The patient’s age
2) The stage of the lymphoma
3) Whether or not the lymphoma is in organs outside the lymph system
4) Performance status (PS) – how well a person can complete normal daily activities
5) The blood (serum) level of (LDH)
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25. LONG TERM COMPLICATIONS
Secondary malignancy
Acute Myelogenous Leukemia
Non Hodgkin lymphoma
Carcinomas of breast , lungs & thyroid
Short stature
Hypothyroidism
Sterility
Dental caries
Sub clinical pulmonary dysfunction
Ischemic heart disease
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26. NON-HODGKIN’S LYMPHOMA
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27. Definition:
The neoplastic transformation of either B or T cell lineages of lymphatic cells.
NHL causes the accumulation of neoplastic cells in both the lymph nodes as well as more often diffusely in extralymphatic organs and the bloodstream.
Absent reed-Sternberg cells.
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28. EPIDEMIOLOGY 60% of all lymphomas in children
8-10% of all malignancies in children between 5-19 yrs of age
Secondary causes of NHL include;
Inherited / acquired immune deficiencies
Viruses
HIV
EBV
Genetic Syndromes
Ataxia Telangiectasia
Bloom syndrome
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29. Risk factors INFECTIONS: Human immunodeficiency virus (HIV)
Epstein-Barr virus (EBV): linked to Burkitt lymphoma.
Helicobacter pylori: Extranodal tissues generating lymphoma include MALT ( Mucosa associated lymphoid tissue)
Human T-cell leukemia/lymphoma virus( HTLV-1)
Hepatitis C virus
Age:
Most people with non-Hodgkin lymphoma are older than 60.
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30. PATHOLOGICAL SUB TYPES OF NHL
Burkitt Lymphoma
40% of NHL
B Cell Origin
Lymphoblastic Lymphoma
30% of NHL
80% T Cell Origin & 20% B Cell Origin
Diffuse Large B Cell Lymphoma
20% of NHL
Anaplastic Large Cell Lymphoma
10% of NHL
70% T Cell Origin
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31. Burkitt Lymphoma

32. Clinical Presentation
Clinical presentation is the same as for Hodgkin lymphoma.
The difference is that Hodgkin is localized to cervical and supraclavicular nodes 80%-90% of the time. Whereas NHL is localized 10-20% of the time.
CNS involvement is more common with NHL.
HIV positive patients often have CNS involvement.
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33. Clinical Presentation
Burkitt Lymphoma
Abdominal Tumor
Head & Neck Disease
Involvement of bone marrow & CNS
Lymphoblastic Lymphoma
Intrathoracic / mediastinal supradiaphragmatic mass
Diffuse Large B Cell Lymphoma
Abdominal Mass
Mediastinal Mass
Anaplastic Large Cell Lymphoma
Primary cutaneous manifestation
Systemic disease ( fever , weight loss)
Dissemination to liver , spleen , lung , mediastinum & skin
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34. Clinical Presentation
Other clinical features include;
Lymphadenopathy
Superior vena cava syndrome
Dyspnea
Abdominal Mass
Intestinal obstruction / intussusception
Ascites
Nasal Stuffiness
Earache
Tonsil enlargement
Localised bone involvement
Acute paraplegia secondary to CNS / spinal cord compression
Tumor Lysis Syndrome
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35. Staging system for Non-Hodgkin lymphoma
Stage Description I A single tumor (extranodal) or single anatomic area (nodal) with the exclusion of mediastinum or abdomen
II A single tumor (extranodal) with regional node involvement two or more nodes areas on the same side of diaphragm Two single (extranodal) tumors with or without the regional node involvement on same side of diaphragm A primary gastrointestinal tract tumor usually in the ileocecal area, with or without involvement of associated mesenteric nodes, which may must bemgrossly ( > 90%) resected
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36. Stage III. Two single tumors (extranodal) on opposite
Stage III Two single tumors (extranodal) on opposite side of the diaphragm Two more nodal areas above and below the diaphragm Any primary intarthoracic tumor (mediastinal, pleural, or thymic) Any extensive primary intra – abdominal disease IV Any of the above, with initial involvement of central nervous system or bone marrow t time of diagnosis
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37. DIFFERENTIAL DIAGNOSIS
Hodgkin Disease
Leukemia
Germ Cell Tumor
Wilms Tumor
Neuroblastoma
Rhabdomyosarcoma
Reactive lymphadenitis
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38. Diagnosis Tissue biopsy for; Flow cytometry Karyotyping
Bone marrow biopsy is more central in the initial staging of NHL
Complete Blood Count
Serum Electrolytes, Calcium , Phosphorus , Uric acid
LFT’s & RFT’s
Bone Marrow Aspiration & Biopsy
CSF Examination
Chest X Ray
CT Scan
Head & Neck
Chest
Abdomen & Pelvis
PET Scan & Bone Scan
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39. Grades NHL divided into Low and high grade
A high grade lymphoma has cells which look quite different from normal cells.
They tend to grow fast (aggressive).usually look follicular. Incurable. Wider dissemination at presentation.
Low grade lymphomas have cells which look much like normal cells and multiply slowly(indolent).usually look diffuse. Long term treatment maybe achievable.
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40. Low-grade lymphomas
Many low-grade lymphomas remain indolent for many years.
Treatment of the non-symptomatic patient is often Avoided.
In this case watchful waiting is often the initial course of action. This is carried out because the harms and risks of treatment outweigh the benefits.
If a low-grade lymphoma is becoming symptomatic, radiotherapy or chemotherapy are the treatments of choice.
They don’t cure the lymphoma, they can alleviate the symptoms.
Patients with these types of lymphoma can live near-normal lifespans, but the disease is Incurable.
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41. High-grade lymphomas
Treatment of the aggressive, forms of lymphoma can result in a cure in the majority of cases.
However, the prognosis for patients with a poor response to therapy is worse.
Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or R-CHOP regimen.
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42. Treatment The initial chemotherapeutic regimen is CHOP
( cyclophosmamide, hydroxy-adriamycine, oncovin and prednisolone).
CNS lymphoma is often treated with radiation in addition to CHOP.
Relapses can be controlled with BM transplantation.
Some pts express CD-20 antigen in greater amount. In this case, monoclonal antibody Rituximab should be used.
Rituximab is an anti-CD20 antibody that has limited toxicity and add survival benefit to the use of CHOP.
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43. Duration of Treatment
Burkitt Lymphoma & Diffuse Large B Cell Lymphoma ………. 6 weeks to 6 months
Lymphoblastic Lymphoma …..24 months
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44. COMPLICATIONS Infections Mucositis Pancytopenia Electrolyte imbalance
Poor nutrition
Growth retardation
Cardiac Toxicity
Gonadal Toxicity with Infertility
Secondary malignancies
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45. Thank you
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