1. LYMPHOMA Hodgkin`s Disease Non-Hodgkin`s Disease
Acibadem University
Acibadem Medical Faculty
Paediatrics Department
Ertugrul Eryilmaz MD
Assistant Professor Paediatrics

2. Lymph System
Lymphoma may affect any of the parts of the lymph system. Most commonly, patients first notice an enlargement of lymph nodes - usually in the neck, groin or armpits.
Lymphomas can occur in other organs as well. This is because small amounts of lymph and lymph tissue pass through practically all organs in the body in order that white blood cells can reach them to control infections.

3. RES
++Timus

4. Lymphoid tissue Two types of lymphoid tissue exist:
Central (bone marrow and thymus) and
Peripheral (blood, spleen,liver, lymph node, and mucosa-associated).
Within central lymphoid tissue, cells arise and differentiate into mature lymphocytes; they then migrate into peripheral lymphoid tissues and recirculate throughout the body

5. Bone marrow Lymphoid tissue CLL MM ALL DLBCL, FL, HL stem cell
DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma; HL Hodgkin Lymphoma, MM Multiple Myeloma ALL Acutel lymphocytic lymphoma; CLL Chronic Lymphoblastic Lymphoma
memory
B-cell
DLBCL,
FL, HL
ALL
CLL MM
stem
cell
germinal
center
B-cell
mature
naive
B-cell
lymphoid
progenitor
progenitor-B
pre-B
immature
B-cell
plasma cell
Bone marrow
Lymphoid tissue

6. Myeloproliferative disorders
ALL MM
CLL
Lymphomas
naïve
germinal center
B-lymphocytes
Plasma
cells
Lymphoid
progenitor
T-lymphocytes
Hematopoietic
stem cell
AML
Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor

7. Proto-Oncogenes / Suppressor Genes
Similar to most human cancers, the genetic lesions involved in non-Hodgkin lymphoma include activation of proto-oncogenes and disruption of tumour suppressor genes

8. Lymphoma
Lymphoma is the third most common cancer in children, with an annual incidence of per million children.
The two broad categories of lymphoma, Hodgkin disease and non-Hodgkin lymphoma (NHL), have such different clinical manifestations and treatments that they are considered separately.

9. Incidence of lymphomas in comparison with other cancers in Canada

10. Hodgkin lymphoma
Thomas Hodgkin
( )

11. Hodgkin Disease Epidemiology
Three forms of Hodgkin disease have been identified in epidemiologic studies: a childhood form (≤ 14 yr of age), a young adult form (15-34 yr of age), and an older adult form (55-74 yr of age).
Hodgkin disease accounts for about 5% of cancers in persons younger than 15 yr of age and for about 15% in persons yr of age,
In industrialized countries the highest rate is in adolescents and young adults, in contrast to developing countries, where the highest rate is in younger children.

12. Hodgkin Disease Epidemiology
The role of Epstein-Barr virus (EBV) is supported by serologic studies and the frequent presence of EBV genome in biopsy material.
Males predominate in patients younger than 10 yr of age at diagnosis, with roughly equal gender incidence in adolescence.
Pre-existing immunodeficiency, either congenital or acquired, increases the risk of developing Hodgkin disease.
A genetic predisposition or a common exposure to the same etiologic agent could account for an apparent increased risk in twins and first-degree relatives ranging from 3- to 7-fold.

13. Age distribution of new Hodgkin lymphoma cases in Canada

14. Pathogenesis
The Reed-Sternberg cell, a large cell (15-45 μm in diameter) with multiple or multilobulated nuclei, is considered the hallmark of Hodgkin disease
There is now general agreement that the Reed-Sternberg cell arises from germinal center B-cells in most cases.

15. Histologic subtypes lymphocyte predominant, nodular sclerosing
mixed cellularity
lymphocyte depleted.
Most cases previously classified as lymphocyte depleted are now considered to represent high-grade non-Hodgkin lymphoma.

16. Pathognomonic

17. Lymphocyte Predominant

18. Reed Sternberg & CD20 (+)

19. Mixed Cellularity

20. Clinical Manifestations
         
Clinical Manifestations
Painless, firm, cervical, or supraclavicular lymphadenopathy is the most common presenting sign.
Inguinal or axillary lymphadenopathy sites are uncommon areas of presentation.
An anterior mediastinal mass is often present and can rapidly disappear with therapy
Clinically detectable hepatosplenomegaly is rarely encountered.
Depending on the extent and location of nodal and extranodal disease, patients might present with symptoms and signs of airway obstruction, pleural or pericardial effusion, hepatocellular dysfunction, or bone marrow infiltration (anemia, neutropenia, or thrombocytopenia).
Nephrotic syndrome is a rare but recognized presenting manifestation of Hodgkin disease

22. Some causes of mediastinal Masses in adults.

23. Some Causes of Mediastinal Masses in Children
Anterior
Ectopic thyroid
Lymphoma
Sarcoma
Teratoma
In thymus:Cyst Histiocytosis Histoplasmosis Normal thymus Thymoma
Middle
Bronchogenic cyst
Cardiac tumor
Cystic hygroma
Lymphadenopathy
Pericardial cyst
Vascular abnormalities
Posterior
Esophageal duplication
Meningomyelocele
Neuroenteric abnormalities
Neurogenic tumors

24. SYMPTOMS Systemic symptoms considered important in staging
Unexplained fever
Weight loss
Drenching night sweats.
Less common non-prognostic significance are
pruritus,
lethargy,
anorexia,
pain that worsens after ingestion of alcohol.
Because of the impaired cellular immunity, concomitant tuberculous or fungal infections may complicate Hodgkin disease and predispose to complications during immunosuppressive therapy.
In the pre-vaccine era varicella-zoster infections occurred at some time during the course of the disease in about 30% of cases.

25. Diagnosis
Any patient with persistent, unexplained lymphadenopathy unassociated with an obvious underlying inflammatory or infectious process should have a chest radiograph to identify the presence of a mediastinal mass before undergoing node biopsy.
Formal excisional biopsy is preferred over needle biopsy to ensure that adequate tissue is obtained,
Hodgkin disease is rarely diagnosed with certainty on frozen section. Ideally, a portion of the biopsy specimen should be frozen and stored to allow for additional studies.

26. Modified Ann Arbor Staging System for Hodgkin Disease*
STAGE I Involvement of a single lymph node region or of a single extralymphatic organ or site
STAGE II Involvement of two or more lymphoid regions on the same side of the diaphragm; or localized involvement of an extralymphatic organ or site and of one or more lymph node regions on the same side of the diaphragm
STAGE III Involvement of lymph node regions on both sides of the diaphragm, which may be accompanied by localized involvement of an extralymphatic organ or site or by splenic involvement
STAGE IV Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node enlargement
*Stages are further categorized as: A or B, based on the absence or presence, respectively, of systemic symptoms of fever and/or weight loss
Bulky disease, based on mediastinal mass larger than one third thoracic diameter; lymph node masses ≥10 cm in diameter and/or four or more nodal regions involved.

27. Staging of lymphoma Stage I Stage II Stage III Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss

28. Studies Necessary for Clinical Staging of Hodgkin Disease
Measurement of palpable lymph nodes, liver, and spleen
Complete blood cell count
Erythrocyte sedimentation rate,
Serum ferritin,
Serum copper
Liver function tests
Chest radiograph with measurement of mediastinal ratio
Chest CT with contrast medium enhancement
Neck CT if high cervical nodes palpable
Abdominal CT or MRI Gallium scan
Bone marrow biopsy with advanced disease or "B" symptoms
Bone scan with elevated serum alkaline phosphatase level and/or bone pain

29. Treatment
Because of concern about late effects, treatment of children in North America and Europe has evolved from primary treatment with extended-field radiation therapy to use of multiagent chemotherapy as the cornerstone of treatment, supplemented in selected cases by relatively low-dose involved-field irradiation (2,000-2,500 cGy).
Treatment is largely determined by disease stage, patient's age at diagnosis, the presence or absence of "B" symptoms, and the presence of hilar lymphadenopathy and/or bulky nodal disease.
Although there is not yet general agreement on their definitions, three risk groups have been identified.
Favorable presentations include stages I and IIA.
Intermediate presentations include stages I, IIB (with symptoms, bulky disease, or hilar lymphadenopathy), and stage IIIA.
Unfavorable presentations include stages IIIB and IV.

30. Chemotherapy The chemotherapy regimens in current use are based on
MOPP (nitrogen mustard [Mustargen], vincristine [Oncovin], procarbazine, and prednisone), or
ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine),
or variations and/or combinations of the two together with additional active agents such as etoposide and methotrexate.
As originally conceived, a minimum of six cycles of chemotherapy was given with significant cumulative toxicity, including
second malignancies,
sterility,
and cardiac
and pulmonary dysfunction.
The long-term toxicity is determined by the total dose of the agents.

31. EORTC risk factors in localised disease
Favourable
Patients must have all features:
Clinical stage 1 and 2
Maximum of three nodal areas involved
Age younger than 50 years
Erythrocyte sedimentation rate (ESR) less than 50 mm/h without B symptoms or
ESR less than 30 mm/h with B symptoms
Mediastinal/thoracic ratio less than 0·35
Unfavourable
Patients have any features:
Clinical stage 2 with involvement of at least four nodal areas
Age older than 50 years
ESR greater than 50 mm/h if asymptomatic or ESR greater than 30 mm/h if B
symptoms
Mediastinal/thoracic ratio greater than 0·35

32. UNFAVORABLE PRESENTATIONS
Chemotherapy, based on the same regimens used in early stage disease, is considered the primary treatment for patients with advanced disease, but the role of radiation is still under study.
Because the cure rate with conventional drug combinations, with or without radiation therapy, is only 60-70%, newer and more aggressive regimens have been developed and are now in clinical trials.

33. RELAPSE
Patients who suffer relapse after initial treatment with radiation alone or after an initial remission of more than 12 mo after chemotherapy alone or combined modality therapy usually respond to additional chemotherapy or radiation or both.
Those who never achieve remission or who suffer relapse after an initial remission of less than 12 mo after chemotherapy or combined modality therapy have a poorer prognosis and are candidates for myeloablative chemotherapy and autologous stem cell or bone marrow rescue.

34. Prognosis
Most treatment programs result in disease-free survival rates of more than 60%, with overall cure rates greater than 90% in those with early stage disease and more than 70% in more advanced cases.
All newly diagnosed cases in children and adolescents should be treated with curative intent; this is consistently and effectively achieved with combined modality therapy. The choice of regimen is then selected on the basis of risk category and observed or anticipated long-term complications. Elimination of routine staging laparotomy and splenectomy avoids concerns about surgical morbidity and postsplenectomy infections.

35. Classical Hodgkin Lymphoma

37. Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma (NHL) results from malignant clonal proliferation of lymphocytes of T-, B-, or indeterminate cell origin.
In the United States, NHL occurs with an annual incidence of 10.5 per million white and 7.3 per million black children younger than 20 yr of age.
In equatorial Africa, 50% of childhood cancers are lymphomas, a result of the very high incidence of Burkitt lymphoma and possibly related to the immunosuppressive effects of malaria. Unlike that of Hodgkin disease, the incidence of NHL increases steadily throughout life.
In some situations there is overlap with acute lymphoblastic or B-cell leukemia. Patients with lymphoblastic NHL and more than 25% lymphoblasts in the bone marrow are arbitrarily classified and treated as if they had acute lymphoblastic leukemia, whereas patients with B-cell ALL are treated similarly to patients with Burkitt lymphoma even if no extramedullary disease is present.

38. Age distribution of new NHL cases in Canada

39. Pathogenesis
EBV infection has a major role in the pathogenesis of Burkitt lymphoma. The EBV genome is present in tumor cells in 95% of "endemic" cases in equatorial Africa compared with 15% in "sporadic" cases in the United States.
How EBV contributes to the pathogenesis of Burkitt lymphoma remains unclear.
Congenital or acquired immunodeficiency also predisposes to the development of NHL.
Epidemiologic studies have also implicated pesticide exposure as a possible risk factor.

40. Classification
Most cases of NHL in children are high-grade, diffuse neoplasms.
Three histologic subtypes are recognized:
lymphoblastic, usually of T-cell origin;
small non-cleaved cell lymphoma (SNCCL), with Burkitt and non-Burkitt subtypes and of B-cell origin
large cell lymphoma (LCL), with diffuse and anaplastic subtypes and of T-, B-, or indeterminate cell origin.
The diagnosis and classification of childhood NHL requires considerable hematopathologic expertise and adequate diagnostic tissue, both fresh and frozen.

41. Chromosomal Translocations
Different chromosomal translocations are specific for some histologic subtypes and involve various proto-oncogenes, resulting in malignant transformation through a variety of mechanisms.
In SNCCL (Burkitt type), one of three chromosomal translocations [t(8;14), t(8;22), t(2;8)] results in approximation of the MYC proto-oncogene on chromosome 8 to a regulatory region of one of the immunoglobulin chain genes, resulting in dysregulation of MYC;
In anaplastic LCL, fusion of the NPM gene on chromosome 5 with the ALK gene on chromosome 2 leads to formation of a chimeric protein that can influence cell growth and proliferation.

42. Clinical Manifestations
Presenting signs and symptoms vary with disease site and extent, and these in turn differ with histologic subtype.
Lymphoblastic NHL often presents as an intrathoracic tumor, usually a mediastinal mass, and is associated with dyspnea, chest pain, dysphagia, pleural effusion, and superior vena cava syndrome. Cervical or axillary lymphadenopathy is present in up to 80% of patients at diagnosis. Primary involvement of bone, bone marrow, testis, or skin is not uncommon. The central nervous system (CNS) may also be involved.
SNCCL presents as an abdominal tumor in 80% of U.S. cases in patients with abdominal pain or distention, bowel obstruction, change in bowel habits, intestinal bleeding, or, rarely, intestinal perforation. Other sites include CNS, bone marrow, and peripheral lymph nodes. Jaw involvement occurs in less than 20% of U.S. cases, compared with 70% of younger patients in equatorial Africa.
LCL occurs in many sites, including the abdomen and mediastinum. Extramedullary sites include skin, bone, and soft tissues. CNS involvement is rare, in contrast to SNCCL and lymphoblastic NHL.

43. LABORATORY FINDINGS
Pretreatment Studies for Staging Pediatric Non-Hodgkin Lymphoma
Complete blood cell count
Serum electrolytes,
Uric acid, lactate dehydrogenase, creatinine, calcium, phosphorus
Liver function tests
Chest radiograph and chest CT if abnormal
Abdominal and pelvic ultrasonography and/or CT
Gallium scan and/or bone scan
Bilateral bone marrow aspirate and biopsy
Cerebrospinal fluid cytology

44. Investigations done before initiation of treatment
Essential procedures
A full history, recording growth rate, symptoms present, performance status
A detailed physical examination, with special attention to all node-bearing areas including Waldeyer’s ring
Adequate surgical biopsy specimen, allowing
immunophenotyping and examined by a skilled pathologist

45. Investigations done before initiation of treatment
Laboratory procedures:
Full blood count, including erythrocyte sedimentation
rate
Serum lactate dehydrogenase, calcium, uric acid,
proteins and electrophoresis, alkaline phosphatase
Assessment of renal and liver function
Radiological studies:
Chest radiograph
Thoracic and abdominal-pelvic CT scan
Bone-marrow aspirate and trephine, to include molecular genetic analysis if available

46. Optional procedures, depending on clinical picture
2 microglobulin
Endoscopy, eg, for gastric MALT lymphoma
Plain radiographs, bone scan, or MRI
Positron electron tomography (PET)
Head or spinal MRI for neurological symptoms
Cerebrospinal fluid analysis in patients at risk

47. Laboratory findings
Laboratory findings vary, depending on sites or organs involved.
Elevated serum uric acid levels and other features of tumor lysis syndrome often complicate the presentation of SNCCL.
Elevated serum level of lactate dehydrogenase is a measure of tumor burden and may occur with any NHL subtype.
A normal CBC does not preclude marrow involvement.
CT or MRI of the chest or abdomen or both provides key information on disease extent.
Surgical staging is not necessary.

48. Symptoms of non-Hodgkin lymphoma needing urgent referral
Lymphadenopathy (>1 cm persisting for 6 weeks)
Hepatosplenomegaly
Three or more of the following symptoms:
Fatigue
Night sweats
Weight loss
Itching
Breathlessness
Bruising
Recurrent infection
Bone pain

49. Diagnosis
Prompt tissue diagnosis and staging is important because of the rapid growth rate of lymphomas, especially SNCCL.
To ensure adequate tissue for accurate diagnosis and subtyping, multiple needle biopsy specimens or a large wedge of tumor should be obtained.
Several studies are necessary to accurately stage the disease and provide baseline measurements of organ function before treatment is instituted
In cases with airway compromise, potential for anesthetic complications, and no easily accessible tissue to sample, empirical therapy may be started using corticosteroids.

50. An algorithm for evaluation and treatment of children with an anterior mediastinal mass.
Figure 7. An algorithm for evaluation and treatment of children with an anterior mediastinal mass. PICU = pediatric intensive care unit; CBC = complete blood count; CT = computerized tomography; CXR = chest radiography; SVC = single-lung ventilation; LP = lumbar puncture.
Hammer G B Anesth Analg 2001;92:
©2001 by Lippincott Williams & Wilkins

51. Diagnosis
The St. Jude staging system defines tumor extent, which is important for designing treatment.
Stage I applies to localized disease, stage II to regional disease (except for mediastinal tumors, which are designated stage III), stage III to extensive disease, and stage IV to disseminated (CNS and/or bone marrow) disease. Elevated levels of serum lactic dehydrogenase (>500 U/L) correlate with tumor mass and have proved useful for stratifying therapy intensity.

52. St. Jude Staging System for Childhood Non-Hodgkin Lymphoma
STAGE I A single tumor (extranodal) or single anatomic area (nodal), with the exclusion of mediastinum or abdomen.
STAGE II A single tumor (extranodal) with regional node involvement. Two or more nodal areas on the same side of the diaphragm. Two single (extranodal) tumors with or without regional node involvement on the same side of the diaphragm. A primary gastrointestinal tract tumor, usually in the ileocecal area, with or without involvement of associated mesenteric nodes only, which must be grossly (>90%) resected.
STAGE III Two single tumors (extranodal) on opposite sides of the diaphragm. Two or more nodal areas above and below the diaphragm. Any primary intrathoracic tumor (mediastinal, pleural, or thymic). Any extensive primary intra-abdominal disease.
STAGE IV Any of the above, with initial involvement of central nervous system and/or bone marrow at time of diagnosis.

53. Staging of lymphoma Stage I Stage II Stage III Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss

54. Treatment and Prognosis
Surgical excision of localized intra-abdominal tumors often precedes the diagnosis of NHL and should always be attempted, if feasible.
In this and other situations, multiagent chemotherapy is the primary treatment.
Tumor lysis syndrome (i.e., high serum potassium, uric acid, and high phosphorus with low calcium levels) frequently complicates initial treatment of disseminated disease. Appropriate hydration with addition of sodium bicarbonate to produce dilute alkaline urine, administration of allopurinol, and correction of electrolyte abnormalities are essential to minimize this life-threatening complication.
In contrast to HD, second malignancies and infertility have not been major problems in long-term survivors of NHL

55. EARLY-STAGE NHL
Unlike HD, NHL is considered a disseminated disease from the time of diagnosis. Even patients with apparently localized and resected disease require chemotherapy.
Patients with stage I/II NHL, irrespective of histologic subgroup, are effectively treated with six cycles of COMP (cyclophosphamide, vincristine [Oncovin], methotrexate, and prednisone) or three cycles of COPA (substituting doxorubicin for methotrexate) followed by 6 mo of mercaptopurine and methotrexate or,
In the case of T-cell lymphoblastic NHL, an acute lymphoblastic leukemia-like regimen. About 90% of cases are cured with these regimens. The emphasis now is on decreasing morbidity of therapy for these children while maintaining the high cure rate.

56. ADVANCED-STAGE NHL
Patients with stage III/IV NHL are best treated with therapy based on the histologic subtype.
Lymphoblastic lymphoma is treated with intensive chemotherapy regimens, generally of 2 yr duration and consisting of multiple chemotherapeutic agents given in cycles or a regimen based on those used for high-risk acute lymphoblastic leukemia.
Cranial radiation, intrathecal chemotherapy, and/or high-dose methotrexate are important for prevention of CNS disease.
Early relapse require cytoablativechemotherapy, and allogenic bone marrow transplantation.

57. ADVANCED-STAGE NHL
SNCCL is treated with relatively short-duration (3-6 mo) intensive chemotherapy regimens, including an alkylating agent (usually cyclophosphamide) coupled with other active systemic agents (vincristine, prednisone, methotrexate, cytarabine, etoposide, and/or doxorubicin) and intrathecal therapy, which produces survival rates of more than 90% in localized and 70-80% in those with disseminated disease.
If relapse occurs, it becomes evident in the 1st yr after diagnosis and is often rapidly progressive and relatively resistant to additional therapy, especially in patients with stage IV disease.
LCL is treated with intensive multiagent chemotherapy regimens similar to those used for lymphoblastic lymphoma, which have produced long-term survival rates of 50-70% in those of T-cell origin. For B cell-derived LCL, short, intensive regimens as outlined earlier for SNCLL have produced 6-yr event-free survival as high as 95%.

58. Extranodal lymphomas
Extranodal lymphomas in general should be treated as for nodal disease.
Aggressive lymphomas are usually treated with combined chemoradiotherapy, producing an 80% 5-year survival, a 20–30% improvement on treatment with radiotherapy alone.
Certain extranodal lymphomas present special clinical management problems.

59. Gastric lymphoma of MALT type
Mucosa-associated lymphatic tissue, or "MALT" lymphoma
Although MALT-type marginal-zone lymphomas arise at other sites (such as salivary gland, lung, and thyroid), gastric MALT lymphomas are uniquely related to previous infection with Helicobacter pylori.
Eradication with appropriate antibiotics results in regression of the lymphoma in three-quarters of patients,
Although fewer than half achieve sustained molecular remission.The 10-year survival is about 90%, although transformation to diffuse large B-cell lymphoma can happen.

60. Lymphoma of the central nervous system
Primary lymphoma of the central nervous system is an aggressive tumour (usually of diffuse large B-cell type) arising in brain, leptomeninges, or eye.
Its prevalence has risen strikingly in the immunocompetent population.
Traditionally, radiotherapy was the treatment of choice, but tumour recurrence was common, and chemotherapy (with high-dose methotrexate-based regimens), combined with irradiation, has strikingly enhanced average survival to up to 5 years.
However, late neurotoxic effects are a typical complication of this approach, and chemotherapy alone is being tested.

61. Testicular lymphoma
Although rare, primary testicular lymphoma is the most frequent testicular malignancy in men older than age 60 years.
Pathology is usually of diffuse large B-cell type, and despite apparently localised presentation, prognosis is worse than with most other sites with the same histological findings.
A high frequency of central nervous system relapse has been noted, so much so that prophylactic intrathecal chemotherapy has been advocated in addition to CHOP and adjuvant radiotherapy.

62. New approaches High-dose chemotherapy
For aggressive lymphoma in first remission
For refractory or relapsed aggressive high-grade lymphoma
For indolent lymphoma
Allogeneic stem-cell transplantation
Radiolabelled monoclonal antibody treatments
Vaccine treatments

63. Radiolabelled monoclonal antibody treatments
Rituximab is a chimeric human-murine IgG1 monoclonal antibody that binds specifically to the B-cell surface antigen CD20
The glycosylated protein consists of the constant regions of human IgGs combined with the variable region from murine IgGs, and is produced by Chinese hamster ovary cells in suspension culture.
The antibody induces both complement-mediated and antibodydependent cytotoxic effects on CD20-positive cells.
It has also been reported to induce apoptosis and sensitise chemoresistant human lymphoma cell lines to cytotoxic chemotherapy.23–25 The antibody is well tolerated and its main toxic effect is either haematological (thrombocytopenia and neutropenia) or infusion-related.
Prevalence of human antichimeric antibody is less than 10%.26–28 It has
important single-agent efficacy, giving remission rates of 40–50% in the treatment of relapsed indolent lymphoma,
Now received UK National Institute for Clinical Excellence approval for patients who have failed standard chemotherapy.

64. Unusual Non-Hodgkin Lymphomas Mycosis fungoides
Mycosis fungoides is a rare, persistent, very slow-growing non-Hodgkin lymphoma.
Most people who develop it are older than 50.
It originates from mature T lymphocytes and first affects the skin.
Mycosis fungoides starts so subtly and grows so slowly that it may not be noticed initially. It causes a long-lasting, itchy rash—sometimes a small area of thickened, itchy skin that later develops nodules and slowly spreads.
In some people, it develops into a form of leukemia (Sézary syndrome). In other people, it progresses to the lymph nodes and internal organs. Even with a biopsy, doctors have trouble diagnosing this disease in its early stages. However, later in the course of the disease, a biopsy shows lymphoma cells in the skin.
The thickened areas of skin are treated with a form of radiation called electron beam or with sunlight and corticosteroids applied to the skin..
On average, people live 7 to 10 years after the diagnosis is made, but survival varies widely depending on how far the cancer has spread. Treatment does not cure the disease, but it slows it down even further.

66. SEZARY SYNDROME/Erythema

67. Unusual Non-Hodgkin Lymphomas Burkitt's lymphoma
Burkitt's lymphoma is a very fast-growing non-Hodgkin lymphoma that originates from B lymphocytes.
Burkitt's lymphoma can develop at any age, but it is most common in children and young adults, particularly males.
Unlike other lymphomas, Burkitt's lymphoma has a specific geographic distribution: It is most common in central Africa and rare in the United States.
Infection with Epstein-Barr virus is associated with Burkitt's lymphoma.
It is more common in people who have AIDS.Burkitt's lymphoma grows and spreads quickly, often to the bone marrow, blood, and central nervous system.
When it spreads, weakness and fatigue often develop.
Large numbers of lymphoma cells may accumulate in the lymph nodes and organs of the abdomen, causing swelling. Lymphoma cells may invade the small intestine, resulting in blockage or bleeding.
The neck and jaw may swell, sometimes painfully.
To make the diagnosis, doctors do a biopsy of the abnormal tissue and order procedures to stage the disease.

69. Indolent (Slow-Growing, Low Grade) Lymphomas
Slow-growing lymphomas are subdivided into numerous B-cell and T-cell subtypes, for example:
B-cell
Small lymphocytic / pro-lymphocytic lymphoma (SLL)
Follicular lymphoma (few large cells)
Lymphoplasmacytoid lymphoma
Marginal zone lymphoma
T-cell
Large granular lymphocyte leukemia
Adult T-cell leukemia/lymphoma (ATL/L )
Mycosis fungoides/Sézary Syndrome

70. INDOLENT LYMPHOMA
A type of lymphoma that tends to grow and spread slowly, and has few symptoms. Also called low-grade lymphoma. lymphoma, usually takes several years to develop.
Follicular lymphoma is typically a slow-growing, or indolent, form of non-Hodgkin lymphoma.
This cancer, which accounts for roughly 20 to 30 percent of all non- Hodgkin 
It usually appears in a lumpy, or nodular pattern, within lymph nodes throughout the body.
Often, the first sign of follicular lymphoma is a painless swelling in the neck, armpit or groin caused by enlarged lymph nodes.
Some people also report loss of appetite and fatigue.
Doctors sometimes suggest watchful waiting for people with indolent lymphoma. People with indolent lymphoma may not have problems that require cancer treatment for a long time.

71. Waldenstrom’s Macroglobulinemia
Waldenstrom’s macroglobulinemia (also known as lympho-plasmacytic lymphoma or immunocytoma) is a rare, slow-growing B-cell lymphoma that occurs in less than 2 percent of people with NHL.
Waldenstrom’s is characterized by a high level of a protein called immunoglobulin M (IgM) in the blood. These high levels of IgM can cause a thickening of the blood (hyperviscosity), resulting in symptoms such as nosebleeds, headaches, dizziness and blurring or loss of vision

72. Angioimmunoblastic T-cell lymphoma
Angioimmunoblastic T-cell lymphoma is a rare, aggressive (fast-growing) T-cell lymphoma that accounts for between 1 percent and 2 percent of all NHL cases.
Symptoms include high fever, night sweats, skin rash and some types of autoimmune disorders, such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), in which the body does not recognize its own cells.
As a result of these autoimmune disorders, the body makes antibodies against and destroys its own cells and tissues, such as platelets (in the case of ITP) and red blood cells (in the case of AIHA).

73. Further Listening 
Contains Podcasts and webcasts about lymphoma
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