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LYMPHOMA. Dr Bruce Covell. Each year in the UK about about 1500 people develop Hodgkin's disease, usually between 15-25 years of age. It can also develop later in life in people over 60. In younger people the numbers of men to women are about the same but overall Hodgkin's affects more men.

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Dr Bruce Covell


Each year in the UK about about 1500 people develop Hodgkin's disease, usually between 15-25 years of age. It can also develop later in life in people over 60. In younger people the numbers of men to women are about the same but overall Hodgkin's affects more men.

Between 7000 and 7500 people develop non-Hodgkin's lymphoma each year. It is more common over the age of 60 and affects slightly more men than women.

At present the cause of most lymphomas is unknown.


Thomas Hodgkin

English physcian and pathologist, born August 17, 1798, in Pentonville, St. James Parish, Middlesex; died April 5, 1866, Jaffa, Palestine [now Tel Aviv-Yafo, Israel].

members of "The Society of Friends"


Defence against Infection

The castle walls-first line of defence is the skin and the mucosa 

The foot soldiers -macrophages Complement, and other immune cells send out chemical messengers to call for reinforcements.

The cavalry-neutrophils -small, short-lived immune cells ,swallow the invaders and kill them

The SAS-Antibodies recognise and stick to foreign material.B lymphocytes exist to produce antibodies.  infection is over, most of the B cells die, but some live on as memory cells.  

The generals-T lymphocytes major histocompatibility complex (MHC), Helper T cells Cytotoxic T cells recognise cells with foreign proteins attached to MHC on their surface and destroy them directly.  


Disease states correlate with stages in normal B-cell development

  • B-CLL
  • FLL
  • BL
  • Mantle Cell lymphoma
  • Marginal Zone lymphoma
  • MALT
  • GALT
  • Hodgkins (?)
  • MGUS
  • Multiple Myeloma
  • Plasmacytoma






Lymphoid tumors that present as mature B-cellsmay have arisen as a result of the interplay between geneticlesions and normal processes that govern lymphoid tolerance,homeostasis and function

a minimalist view of a t cell response





















A minimalist view of a T cell response


elimination of infection


activation and proliferation


apoptosis and memory




“Nowhere in pathology has a chaos of names clouded clear concepts as inthe subject of lymphoid tumors”

Willis R.A.: Pathology of tumors, Mosby 1948






Non Hodgkins

B Cells Nodular sclerosing 50%

Mixed cellularity –30-40%

T Cells



% Of Lymphomas

Age of Incidence



With appropriate treatment, more than 80% of people with stage I or II Hodgkin's survive for at least 10 years. With widespread disease, the treatment is more intense and the 5-year survival rate is about 60%.1.

Classical •

Nodular sclerosing -  

50% commonest of all types of Hodgkin's lymphoma.

Commonest in women in their 20’s and 30’s.

less favourable prognosis than the lymphocyte predominant

usually picked up at an early stage from enlarged lymph nodes in the neck.

Mixed cellularity - .

30 – 40%-

Commonest in older people.

•Lymphocyte depleted


worst prognosis

Lymphocyte-rich –


2. Nodular lymphocyte predominance


most favourable prognosis

'popcorn' cells.


 B Cell lymphoma

% Of Lymphomas

Age of Incidence



Diffuse large B-cell lymphoma (DLBCL):



40% to 50% are cured

fast growing

2 kinds Genetics One serious

Follicular lymphoma


60. rare in very young

5-year survival rate60% to 70%.

slow growing

can (transform) into a fast growing diffuse B-cell lymphoma.

Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL):


live well over 10 years

not considered curable

are slow growing can transform into a more aggressive type of lymphoma

Mantle cell lymphoma:


Men most often affected. average age 63

very serious. 20% of patients survive at least 5 years.

Extranodal marginal zone B-cell lymphomas - mucosa-associated lymphoid tissue (MALT) lymphomas


average age about 60

slow growing lymphoma often curable in its early stages.

stomach Helicobacter pylori.

Nodal marginal zone B-cell lymphoma:


slow growing cured if diagnosed in early stages.

cells are small.

Splenic marginal zone B-cell lymphoma


often elderly and male

slow growing,

Primary mediastinal B-cell lymphoma


two thirds women. 30s.

About half of patients can be cured. fast growing

mediastinum closely related to Hodgkin disease

Burkitt lymphoma:


90% of patients are male, and the average age is about 30

half of patients are cured by aggressive chemotherapy.

medium size fast growing African jaws d US, abdomen,

Lymphoplasmocytic lymphoma (Waldenstrom macroglobulinemia


not curable, most live longer than 5 years.

slow growing Thick blood Symptoms

Hairy cell leukemia:


Patients are older in general.

slow growing, some patients never need treatment

Primary central nervous system (CNS) lymphoma:


patients with AIDS

poor. 30% 5 years.

called primary brain lymphoma

B-Cell Lymphomas


% Of Lymphomas

Age of Incidence



Precursor T-lymphoblastic lymphoma/leukaemia:


(75%) men, average age 25

No bone marrow cure quite good. involve bone marrow, 20% cured.

lymphoma or leukaemia. fast growing,

Peripheral T-cell lymphomas:,


There are several kinds of peripheral T-cell lymphomas

Cutaneous T-cell lymphoma (mycosis fungoides, Sezary syndrome):


50s or 60s

survival at 5 years ranges 58% slow-growing lymphomas 5% faster growing ones

Skin Sezary syndrome spread all over the body OR mushroom-like (so first named mycosis fungoides

Angioimmunoblastic T-cell lymphoma:

Extranodal natural killer/T-cell lymphoma, nasal type

Enteropathy type T-cell lymphoma

outlook is poor

Coeliac disease

Subcutaneous panniculitis-like T-cell lymphoma

cannot be cured

Anaplastic large T/null-cell lymphoma




T Cell Lymphoma

T-Cell Lymphomas


Hodgkin's Lymphoma VS

Non-Hodgkin's Lymphomas


Average age is 27.7 with two age peaks, the major one between 15 and 24 with a lesser peak after age 55.

Average age is about 67. 

Chance of getting in all people over an entire lifetime

Men 0.23%Women 0.20%

Men 2.12%Women 1.79%


About 15% of all lymphomas

About 85% of all lymphomas


The disease occurs most often in lymph nodes above the collar bone. In Hodgkin's it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients.Only about 15% to 20% of cases are found in areas below the diaphragm.Disease occurs outside the nodes in about 4% of cases.

In NHL it is more likely to appear in the nodes in the abdomen (called the mesenteric nodes).The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.)Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow.

Affected Lymph Cells

B-Lymphocytescharacterized by the Reed-Sternberg Cell

B-Lymphocytes, T-Lymphocytes or Natural Killer (NK) Cells depending on the subtype


More likely than NHL (40%) to have systemic ("B") symptoms (such as fever and night sweats) at the time of diagnosis.

Less likely than HL to have systemic ("B") symptoms (27%) at the time of diagnosis.


Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.

More likely than HD to be diagnosed in stage IV (36%) but this will vary by NHL subtype. 

The Non-Hodgkin's lymphomas are less predictable in their course than Hodgkin's and they are more apt to spread.


Lymphoma Symptoms

  • (Hodgkin's Disease = HL, or a form of Non-Hodgkin's Lymphoma = NHL):
    • Lymph node swelling, often in the upper body area but it can be in almost any node or related organ.  The node is usually NOT painful as opposed to infected lymph nodes which are common and can be painful (HL, NHL)
    • A lack of energy, general fatigue. (HL, NHL) 
    • Weight loss - usually at least 10% over a short time (HL, NHL)
    • Fevers which can come and go.  This can be accompanied by chills or a feeling of temperature swings (HL, NHL)
    • Night sweats - unexplained sweating at night, often drenching (more often HL than NHL)
    • Itching - itching without an apparent cause or rash, sometimes deep in the skin rather than on the surface, sometimes on different parts of the body (more often HL than NHL)
  • Less Often:
    • Some people have lower back pain that is unexplained (may be caused by expanding lymph nodes pressing on nerves). (HL, NHL)
    • Lymph nodes are possibly painful after alcohol consumption. (HL)
  • What now?
  • A good percentage of diagnoses are made during routine tests, x-rays, or even while pregnant.  This is how difficult it is to diagnose lymphoma based on external symptoms alone
staging defines how widespread the disease is and the locations of the disease in the body
Staging defines how widespread the disease is and the locations of the disease in the body.

Anne Arbor staging for Hodgkin's disease -


Extranodal notations 

Extranodal means 'beyond nodal' -  sites are identified by the following notation: 


ANN ARBOR notations 

Ann Arbor staging further classifies patients with lymphoma into A or B categories:

A = without symptoms

B = with symptoms including unexplained weight loss (10% in 6 months prior to diagnosis,  unexplained fever, and drenching night sweats. 

Disease Staging may also be accompanied by local involvement of an extranodal organ or site.

Example involving spleen and Ann Arbor notation: Stage IIIS A


TreatmentLymphomas are usually treated by a combination of chemotherapy, radiation, surgery, and/or bone marrow transplants. The cure rate varies greatly depending on the type of lymphoma and the progression of the disease.


Current up-front treatment regimens for aggressive lymphomas

(Used at various doses, with, or without radiation)


Additional experimental therapies for B-cell lymphomas:

  • CD20-specific antibodies (Rituximab, Bexxarr, Zevalin):target a tetraspanin on the surface of all B-cells and ablatesthe entire B-cell compartment for over 6 months. Mechanismof action is unknown. Rarely used as up-front therapy.
  • Clonotypic antibodies to individual lymphomas: pioneeredby Ron Levy and his colleagues at Stanford. Current successrate is 1 patient in 15 years.

Evidence for a possible role of outside agent in lymphomagenesis:

  • pristane-induced plasmacytomas in mice and rats (Andreson and Potter, 1969)
  • Retroviral infection of mice elicits T-cell lymphomas only in those strains that couldmount an immune response to the virus (McGrath and Weissman, 1979, Lee andIhle, 1981)
  • Infection with Helicobacter pylori correlates well with MALT lymphoma - antibiotictreatment leads to remission in these patients (Casella et al, 2001).
  • Long-term untreated chronic GVHD after transplantation (Gleichmannand Gleichmann, 1971)
  • Large B-cell lymphomas (DLBCL, FLL, BL) have been shown to express Igmolecules on their surface, which bear the scars of affinity maturation; anantigen-driven process (Klein et al, 1995, Chapman et al, 1995, Kuppers et al, 1997)
  • The gene expression profiles of DLBCL cells resemble those of B-cells thathave mounted a response to antigen (Alizadeh et al, 2000).
  • These findings prompt the hypothesis that an antigenic stimulus may cooperatewith other tumorigenic influences in the genesis of lymphoid tumors

Autoimmunity and lymphoid neoplasia may represent differentparts of a single disease-spectrum:

  • Patients who suffer from several autoimmune syndromes are50-200 fold more likely to develop B-cell lymphomas(Sjörgen’s syndrome, autoimmune thyroditis, autoimmune hemolyticanemia, systemic lupus erythematosus, rheumatoid arthritis)
  • Patients who develop the HTLV-1 associated tropical spastic parapesisare also highly prone to develop T-cell lymphomas.
  • Patients with NHL have been found to have high titers of
  • autoantibodies in their sera, and accompanying symptoms, such
  • as autoimmune hemolytic anemia.
  • EBV infection correlates with some autoimmune diseases,
  • such as Hashimoto’s thyroditis.
  • Key differences: clonality of expanded population, disease grade, site ofanatomical presentation, FACS pattern, histopathology