Hodgkin's lymphoma

Dear patients 

Today I have enclosed a link to Hodgkins lymphoma from wikipedia. 

This was the best data I think that is applicable to you. Please note CAPITALS are my comments.

Hodgkin's lymphoma

Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, 
which is a cancer originating from white blood cells called lymphocytes. 
It was named after Thomas Hodgkin, who first described abnormalities in the lymph system in 1832.^[1][2]
 Hodgkin's lymphoma is characterized by the orderly spread of disease from one lymph node group to another and
 by the development of systemic symptoms with advanced disease. 
When Hodgkins cells are examined microscopically, multinucleated Reed-Sternberg cells (RS cells) 
are the characteristic histopathologic finding. 
Hodgkin's lymphoma may be treated with radiation therapy, chemotherapy or Hematopoietic stem cell transplantation,
 the choice of treatment depending on the age and sex of the patient and the stage, 
bulk and histological subtype of the disease.

The disease occurrence shows two peaks: the first in young adulthood (age 15–35) and 
the second in those over 55 years old.^[3]

The 10-year overall survival rate is more than 90% for early stage (stage I or II) Hodgkin's lymphoma. 
Since many patients are young, they often live 40 years or more after treatment. 
However, few studies follow patients as long as 25 years, and 
those studies are of older treatments with more life-threatening adverse effects, 
so it is impossible to predict long-term outcomes of newer, less-harmful treatments. 
Radiation treatments, and some chemotherapy drugs, pose a risk of causing potentially fatal secondary cancers, 
heart disease, and lung disease 40 or more years later. 
Modern treatments greatly minimize the chances of these late effects.^[4]

Patients with a history of infectious mononucleosis due to Epstein-Barr virus may have an increased risk of HL.

Classification

[edit]Types

Classical Hodgkin's lymphoma (excluding nodular lymphocyte predominant Hodgkin's lymphoma) 
can be subclassified into 4 pathologic subtypes based upon Reed-Sternberg cell morphology and 
the composition of the reactive cell infiltrate seen in the lymph node biopsy specimen 
(the cell composition around the Reed-Stenberg cell(s)).

Name	Description	ICD-10	ICD-O
Nodular sclerosing CHL	Is the most common subtype and is composed of large tumor nodules  showing scattered lacunar classical RS cells  set in a background of reactive lymphocytes, eosinophils and plasma cells  with varying degrees of collagen fibrosis/sclerosis.	C81.1	M9663/3
Mixed-cellularity subtype	Is a common subtype and is composed of numerous classic RS cells  admixed with numerous inflammatory cells including lymphocytes,  histiocytes, eosinophils, and plasma cells. without sclerosis.  This type is most often associated with EBV infection and  may be confused with the early, so-called 'cellular' phase of nodular sclerosing CHL.	C81.2	M9652/3.
Lymphocyte-rich or  Lymphocytic predominance	Is a rare subtype, show many features which may cause diagnostic confusion with nodular  lymphocyte predominant B-cell Non-Hodgkin's Lymphoma (B-NHL).  This form also has the most favorable prognosis.	C81.0	M9651/3
Lymphocyte depleted	Is a rare subtype, composed of large numbers of often pleomorphic RS cells with only few  reactive lymphocytes which may easily be confused with diffuse large cell lymphoma.  Many cases previously classified within this category would now be reclassified under  anaplastic large cell lymphoma.[5]	C81.3	M9653/3
Unspecified		C81.9	M9650/3

Lymph node biopsy showing Hodgkin's lymphoma, mixed-cellularity type.

Nodular lymphocyte predominant Hodgkin's lymphoma expresses CD20, 
and is not currently considered a form of classical Hodgkin's.

For the other forms, although the traditional B cell markers (such as CD20) 
are not expressed on all cells,^[5] Reed-Sternberg cells are usually of B cell origin.^[6][7] 
Although Hodgkin's is now frequently grouped with other B cell malignancies, 
some T cell markers (such as CD2 and CD4) are occasionally expressed.^[8] 
However, this may be an artifact of the ambiguity inherent in the diagnosis.

Hodgkin's cells produce Interleukin-21 (IL-21), which was once thought to be exclusive to T cells. 
This feature may explain the behavior of classical Hodgkin's lymphoma, 
including clusters of other immune cells gathered around HL cells (infiltrate) in cultures.^[9]

[edit]Staging

CT image of a 46 year old patient with Hodgkin's lymphoma, image at neck height. On the left side of the patient's neck enlarged lymph nodes are visible (marked in red).

The staging is the same for both Hodgkin's as well as non-Hodgkin's lymphomas.

After Hodgkin's lymphoma is diagnosed, a patient will be staged: 
that is, they will undergo a series of tests and procedures that will determine 
what areas of the body are affected. 
These procedures will include documentation of their histology, 
a physical examination, blood tests, chest X-ray radiographs, 
computed tomography (CT) scans or magnetic resonance imaging (MRI) scans of the chest, 
abdomen and pelvis, and a bone marrow biopsy. 
Positron emission tomography (PET) scan is now used instead of the gallium scan for staging. 
In the past, a lymphangiogram or surgical laparotomy 
(which involves opening the abdominal cavity and visually inspecting for tumors) were performed. 
Lymphangiograms or laparotomies are very rarely performed, 
having been supplanted by improvements in imaging with the CT scan and PET scan.

On the basis of this staging, the patient will be classified according to a staging classification 
(the Ann Arbor staging classification scheme is a common one):

• Stage I is involvement of a single lymph node region (I) 
• (mostly the cervical region) or single extralymphatic site (Ie);
• Stage II is involvement of two or more lymph node regions on the same side of the diaphragm (II) 
• or of one lymph node region and a contiguous extralymphatic site (IIe);
• Stage III is involvement of lymph node regions on both sides of the diaphragm, 
• which may include the spleen (IIIs) and/or limited contiguous extralymphatic organ or site (IIIe, IIIes);
• Stage IV is disseminated involvement of one or more extralymphatic organs.

The absence of systemic symptoms is signified by adding 'A' to the stage; 
the presence of systemic symptoms is signified by adding 'B' to the stage. 
For localized extranodal extension from mass of nodes that does not advance the stage, subscript 'E' is added.

Signs and symptoms

Patients with Hodgkin's lymphoma may present with the following symptoms:

• Night Sweats
• Unexplained weight loss
• Lymph nodes: the most common symptom of Hodgkin's is the painless 
• enlargement of one or more lymph nodes. 
• The nodes may also feel rubbery and swollen when examined. 
• The nodes of the neck and shoulders (cervical and supraclavicular) are most frequently 
• involved (80–90% of the time, on average). 
• The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph.
• Splenomegaly: enlargement of the spleen occurs in about 30% of people with Hodgkin's lymphoma. 
• The enlargement, however, is seldom massive and the size of the spleen may fluctuate 
• during the course of treatment.
• Hepatomegaly: enlargement of the liver, due to liver involvement, is present in about 5% of cases.
• Hepatosplenomegaly: the enlargement of both the liver and spleen caused by the same disease.
• Pain
• Pain following alcohol consumption: classically, 
• involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon.^[10]
• Back pain: nonspecific back pain 
• (pain that cannot be localized or its cause determined by examination or scanning techniques) 
• has been reported in some cases of Hodgkin's lymphoma. 
• The lower back is most often affected.
• Red-coloured patches on the skin, easy bleeding and petechiae due to low platelet count 
• (as a result of bone marrow infiltration, increased trapping in the spleen etc. – 
• i.e. decreased production, increased removal)
• Systemic symptoms: 
• about one-third of patients with Hodgkin's disease may also present with systemic symptoms, 
• including low-grade fever; night sweats; 
• unexplained weight loss of at least 10% of the patient's total body mass in six months or less, 
• itchy skin (pruritus) due to increased levels of eosinophils in the bloodstream; or
•  fatigue (lassitude). 
• Systemic symptoms such as fever, night sweats, and weight loss are known as B symptoms; 
• thus, presence of fever, weight loss, and night sweats indicate that the patient's stage is, 
• for example, 2B instead of 2A.^[11]
• Cyclical fever: patients may also present with a cyclical high-grade fever known as the Pel-Ebstein fever,^[12] 
• or more simply "P-E fever". 
• However, there is debate as to whether or not the P-E fever truly exists.^[13]

Cause

There are no guidelines for preventing Hodgkin's lymphoma 
because the cause is unknown or multifactorial. 
A risk factor is something that statistically increases your chance of getting a disease or condition. 
Risk factors include:

• Sex: male^[14]
• Ages: 15–40 and over 55^[14]
• Family history^[14]
• History of infectious mononucleosis or infection with Epstein-Barr virus, 
• a causative agent of mononucleosis^[14]
• Weakened immune system, including infection with HIV or the presence of AIDS^[14]
• Prolonged use of human growth hormone^[14]
• Exotoxins, such as Agent Orange

Pathogenesis

Diagnosis
Hodgkin's lymphoma must be distinguished from non-cancerous causes of lymph node swelling 
(such as various infections) and from other types of cancer. 
Definitive diagnosis is by lymph node biopsy (Usually excisional biopsy with microscopic examination). 
Blood tests are also performed to assess function of major organs and to assess safety for chemotherapy. 
Positron emission tomography (PET) is used to detect small deposits that do not show on CT scanning. 
PET scans are also useful in functional imaging 
(by using a radiolabeled glucose to image tissues of high metabolism). 
In some cases a Gallium Scan may be used instead of a PET scan.

Pathology

Macroscopy

Affected lymph nodes (most often, laterocervical lymph nodes) are enlarged, 
but their shape is preserved because the capsule is not invaded. 
Usually, the cut surface is white-grey and uniform; in some histological subtypes 
(e.g. nodular sclerosis) a nodular aspect may appear.

A fibrin ring granuloma may be seen.

Microscopy

Variants:
Characteristics of classic Reed-Sternberg cells include large size (20–50 micrometres), 
abundant, amphophilic, finely granular/homogeneous cytoplasm; 
two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and 
a thick nuclear membrane (chromatin is distributed at the cell periphery).

• Hodgkin cell (atypical mononuclear RSC) is a variant of RS cell, 
• which has the same characteristics, but is mononucleated.
• Lacunar RSC is large, with a single hyperlobated nucleus, multiple, 
• small nucleoli and eosinophilic cytoplasm which is retracted around the nucleus,
•  creating an empty space ("lacunae").
• Pleomorphic RSC has multiple irregular nuclei.
• "Popcorn" RSC (lympho-histiocytic variant) is a small cell, 
• with a very lobulated nucleus, small nucleoli.
• "Mummy" RSC has a compact nucleus, no nucleolus and basophilic cytoplasm.

Hodgkin's lymphoma can be sub-classified by histological type. 
The cell histology in Hodgkin's lymphoma is not as important as it is in non-Hodgkin's lymphoma: 
the treatment and prognosis in classic Hodgkin's lymphoma usually depends on the stage 
of disease rather than the histotype.

Management

Patients with early stage disease (IA or IIA) are effectively treated with radiation therapy or chemotherapy. 
The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. 
Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. 
Patients of any stage with a large mass in the chest are usually treated with combined 
chemotherapy and radiation therapy.

ABVD	Stanford V	BEACOPP
Currently, the ABVD  chemotherapy regimen is  the standard treatment of  Hodgkin's disease in the US.  The abbreviation stands  for the four drugsAdriamycin,  bleomycin, vinblastine,  and dacarbazine.  Developed in Italy in the 1970s,  the ABVD treatment typically takes  between six and eight months,  although longer treatments  may be required.	The newer Stanford Vregimen  is typically only half as long  as the ABVD but involves a  more intensive chemotherapy  schedule and incorporates  radiation therapy. In a  randomized controlled  study in Italy, Stanford V  was inferior to ABVD.[15]	BEACOPP is a form of  treatment for stages >  II mainly used in Europe.  The cure rate with  the BEACOPP  esc. regimen is  approximately 10–15%  higher than with standard  ABVD in advanced stages.  This was shown in a paper in  The New England Journal of  Medicine (Diehl et al.),  but US physicians still  favor ABVD, maybe  because some physicians  think that BEACOPP  induces more secondary  leukemia.  However, this seems negligible  compared to the higher cure rates.  BEACOPP is more expensive  because of the requirement for  concurrent treatment with GCSF  to increase production of white  blood cells. Currently, the  German Hodgkin Study Group  tests 8 cycles (8x) BEACOPP  esc vs. 6x BEACOPP esc vs.  8x BEACOPP-14 baseline (HD15-trial).[16]
Doxorubicin	Doxorubicin	Doxorubicin
Bleomycin	Bleomycin	Bleomycin
Vinblastine	Vinblastine, Vincristine	Vincristine
Dacarbazine	Mechlorethamine	Cyclophosphamide,  Procarbazine
	Etoposide	Etoposide
	Prednisone	Prednisone

It should be noted that the common non-Hodgkin's treatment, 
rituximab (which targets CD-20) is not used to treat Hodgkin's 
due to the lack of CD-20 surface antigens in Hodgkin's.

Although increased age is an adverse risk factor for 
Hodgkin's lymphoma, in general elderly patients 
without major comorbidities are sufficiently fit to
 tolerate standard therapy, and have a treatment outcome 
comparable to that of younger patients. 
However, the disease is a different entity in older patients 
and different considerations enter into treatment decisions.^[17]

For Hodgkin's lymphomas, radiation oncologists typically 
use external beam radiation therapy (sometimes shortened to EBRT). 
Radiation oncologists deliver external beam radiation therapy 
to the lymphoma from a machine called a linear accelerator. 
Patients usually describe treatments as painless and 
similar to getting an X-ray. 
Treatments last less than 30 minutes each, every day 
but Saturday and Sunday.

For lymphomas, there are a few different ways radiation 
oncologists target the cancer cells. 
Involved field radiation is when the radiation oncologists 
give radiation only to the parts of your body known to have the cancer.
 Very often, this is combined with chemotherapy. 
Radiation therapy directed above the diaphragm to the neck, 
chest and/or underarms is called mantle field radiation. 
Radiation to below the diaphragm to the abdomen, spleen and/or pelvis 
is called inverted-Y field radiation. 
Total nodal irradiation is when your doctor gives radiation 
to all the lymph nodes in the body to destroy cells that may have spread.^[18]

The high cure rates and long survival of many patients with 
Hodgkin's lymphoma has led to a high concern with late adverse 
effects of treatment, including cardiovascular disease and 
second malignancies such as acute leukemias, lymphomas, and 
solid tumors within the radiation therapy field. Most patients with 
early stage disease are now treated with abbreviated chemotherapy and
 involved-field radiation therapy rather than with radiation therapy alone. 
Clinical research strategies are exploring reduction of the duration of 
chemotherapy and dose and volume of radiation therapy in an attempt 
to reduce late morbidity and mortality of treatment while maintaining 
high cure rates. Hospitals are also treating those who respond 
quickly to chemotherapy with no radiation.

Prognosis

Treatment of Hodgkin's disease has been improving 
over the past few decades. Recent trials that have made 
use of new types of chemotherapy have indicated higher 
survival rates than have previously been seen. In one recent 
European trial, the 5-year survival rate for those patients with 
a favorable prognosis was 98%, while that for patients with worse 
outlooks was at least 85%.^[19]

In 1998, an international effort^[20] identified seven prognostic 
factors that accurately predict the success rate of conventional
 treatment in patients with locally extensive or advanced stage 
Hodgkin's lymphoma. Freedom from progression (FFP) at 5 years 
was directly related to the number of factors present in a patient. 
The 5-year FFP for patients with zero factors is 84%. Each additional 
factor lowers the 5-year FFP rate by 7%, such that the 5-year FFP for
 a patient with 5 or more factors is 42%.

The adverse prognostic factors identified in the international study are:

• Age ≥ 45 years
• Stage IV disease
• Hemoglobin < 10.5 g/dl
• Lymphocyte count < 600/µl or < 8%
• Male
• Albumin < 4.0 g/dl
• White blood count ≥ 15,000/µl

Other studies have reported the following to be the most important 
adverse prognostic factors: mixed-cellularity or lymphocyte-depleted 
histologies, male sex, large number of involved nodal sites, advanced 
stage, age of 40 years or more, the presence of B symptoms, high 
erythrocyte sedimentation rate, and bulky disease (widening of the mediastinum 
by more than one third, or the presence of a nodal mass measuring 
more than 10 cm in any dimension.)

[edit]Epidemiology

Age-standardized death from lymphomasand multiple myeloma per 100,000 inhabitants in 2004.^[21]

     no data     less than 1.8     1.8–3.6     3.6–5.4     5.4–7.2     7.2–9     9–10.8     10.8–12.6     12.6–14.4     14.4–16.2     16.2–18     18–19.8     more than 19.8

Unlike some other lymphomas, whose incidence increases with age, 
Hodgkin's lymphoma has a bimodal incidence curve; that is, 
it occurs most frequently in two separate age groups, 
the first being young adulthood (age 15–35) and
 the second being in those over 55 years old although these peaks 
may vary slightly with nationality.^[22] 
Overall, it is more common in males, except for the nodular sclerosis 
variant, which is slightly more common in females. 
The annual incidence of Hodgkin's lymphoma is about 1 in 25,000 people, 
and the disease accounts for slightly less than 1% of all cancers worldwide.

The incidence of Hodgkin's lymphoma is increased in patients 
with HIV infection.^[23] In contrast to many other lymphomas associated 
with HIV infection it occurs most commonly in patients with higher CD4 T cell counts.

History

Hodgkin's lymphoma was first described in an 1832 report by Thomas Hodgkin,
 although Hodgkin noted that perhaps the earliest reference to the condition 
was provided by Marcello Malpighi in 1666.^[1][2] 
While occupied as museum curator at Guy's Hospital, 
Hodgkin studied seven patients with painless lymph node enlargement. 
Of the seven cases, two were patients of Richard Bright, one was of Thomas Addison, 
and one was of Robert Carswell.^[1] 
Carswell's report of this seventh patient was accompanied by numerous illustrations 
that aided early descriptions of the disease.^[24]

Hodgkin's report on these seven patients, entitled 
"On some morbid appearances of the absorbent glands and spleen", 
was presented to the Medical and Chirurgical Society in London in January 1832 
and was subsequently published in the society's journal, 
Medical-Chirurgical Society Transactions.^[1] 
Hodgkin's paper went largely unnoticed, however, even despite 
Bright highlighting it in an 1838 publication.^[1] 
Indeed, Hodgkin himself did not view his contribution as particularly significant.^[25]

In 1856, Samuel Wilks independently reported on a series of patients with the 
same disease that Hodgkin had previously described.^[25] 
Wilks, a successor to Hodgkin at Guy's Hospital, 
was unaware of Hodgkin's prior work on the subject. 
Bright made Wilks aware of Hodgkin's contribution and in 1865, 
Wilks published a second paper, entitled 
"Cases of enlargement of the lymphatic glands and spleen", 
in which he called the disease "Hodgkin's disease" in honor of his predecessor.^[25]

Theodor Langhans and WS Greenfield first described the microscopic 
characteristics of Hodgkin's lymphoma in 1872 and 1878, respectively.^[1] 
In 1898 and 1902, respectively, Carl Sternberg and Dorothy Reed 
independently described the cytogenetic features of the malignant 
cells of Hodgkin's lymphoma, now called Reed-Sternberg cells.^[1]

Tissue specimens from Hodgkin's seven patients remained at Guy's Hospital 
for a number of years. 
Nearly 100 years after Hodgkin's initial publication, histopathologic 
reexamination confirmed Hodgkin's lymphoma in only three of seven of these 
patients.^[25] 
The remaining cases included non-Hodgkin lymphoma, tuberculosis, and syphilis.^[25]

Hodgkin's lymphoma was one of the first cancers which 
could be treated using radiation therapy and, later, it was one of the first to be treated by 
combination chemotherapy.