Lymphoma: Guidelines at Diagnosis

 For the Newly diagnosed

This topic is for anyone who has just been diagnosed - or just prior to the diagnostic evaluation.  It is also for caregivers -- loved ones who will help the loved to navigate the diagnosis, treatments, and the related decisions to be made.

A lymphoma can be a serious disease, but it is also effectively treatable even at a very advanced stage. Some types of lymphoma are readily cured, other types can be managed well as needed.

The rarer sub types require more attention than most diseases since experience and therefore expertise is less common, so you may need to get more involved with your diagnosis (seeking a second evaluation) and treatment (considering clinical trials) and also seek an expert at a major academic institution to work with your treating physician.

For the indolent lymphomas it can be more likely that you will die with the lymphoma than from it. So let's get started on your new study project. Here are the steps we recommend you take as soon as possible.

See also Encouragement for genuine science- and evidence-based reasons to be hopeful.

Stress and Worry Before the Diagnosis

The stress and worry prior to a diagnosis can be overwhelming. Enlarged lymph nodes can raise concerns about cancer and lymphoma - despite the fact that in most cases enlarged lymph glands are caused by infections that go away with time or with treatment of the infection. 

The Internet can make our anxiety worse, much worse, because the quality and accuracy of the information it provides can be uneven, or plain wrong.  

... The website might not report that there are other and more common causes for enlarged lymph nodes, or for a rash, or for night sweats that concern you.  The website resource may not explain that lymphoma is rare in young persons - making an alternate diagnosis much more likely. 

There is no certainty in life.  That said, prior to the diagnostic test there is good reason to be hopeful that the symptoms that concern you are NOT caused by a lymphoma.  Here are some of the key points to keep in mind:

• The symptoms and signs of lymphoma are common to many medical conditions.
• Younger age decreases the odds that you have a non-Hodgkins lymphoma which affects mainly older persons - median age is about 65 years.
• Hodgkins occurs in young people, but the incidence is low - "The age-adjusted incidence rate was 2.8 per 100,000 men and women per year. These rates are based on cases diagnosed in 2004-2008 from 17 SEER geographic areas.")
• When a lymphoma does occur it rarely presents as a medical emergency - there is in most cases ample time to get the diagnosis right.   Lymphoma is also treatable. 
• When discussing the symptoms that you have with your doctor, first write them down in a concise manner - in the order that the symptoms appeared. Then prepare and rehearse your story

Lymphadenopathy 

refers to lymph nodes that are abnormal in either size

(greater than 1 centimeter), consistency or number." ... classified as:

• Generalized - if lymph nodes are enlarged in two or more separate areas of the body
  OR
  Localized - if only one area is involved." (less suspicious)

• Enlarged lymph glands are common, so don't rush to judgment!
  "Although the finding of lymphadenopathy sometimes raises fears about serious illness, it is, in patients seen in primary care settings, usually a result of  benign (not cancer) infectious causes."
• "A three- to four-week period of observation is prudent in patients with localized nodes and a benign clinical picture."  
• Antibiotic therapy is sometimes tried first, before a biopsy. However, be aware, only bacterial infections will respond to antibiotics. Therefore, if the lymph nodes remain enlarged it may not be a cancer.

Increasing suspicion of a cancer - the need for a biopsy:

• Generalized lymphadenopathy that persists (not limited to one area)
• "Supraclavicular nodes are the most worrisome for malignancy." 
  Source: American Family Physician
• Any painless node that persists for 1-2 months.

"When a node biopsy is indicated, an excisional biopsy (removing the entire lymph node)  of the most abnormal node will best enable the pathologist to determine a diagnosis."

Can a blood test show evidence of lymphoma?

• Rarely.  In almost all cases a biopsy is needed.
  In most cases, a full excisional biopsy is preferred when a biopsy is needed - a fine-needle aspiration (FNA) can be insufficient to get an accurate initial diagnosis.

The Biopsy

A biopsy is the taking of a sample of the cells (from blood or most commonly from tissue) for diagnostic or scientific evaluation.  This can be done with a needle or by surgical removal of a lymph node or lesion.  

A biopsy is essential in order to exclude or diagnose a lymphoma.  The tests done on the sample are also needed to determine the type of lymphoma and the grade, which is required in order to guide the approach to therapy.  A full excisional biopsy (not a needle biopsy) increases the accuracy of the diagnosis, such as to determine the growth pattern (diffuse / nodular) and grade (high or low).

If it is feasible for you, we recommend that you go to a research center that can snap-freeze a portion of the tissue for advanced diagnostics and research, which is vital to making progress against lymphomas.  Seek NCI-Designated Cancer Centers 

Finally, it is good practice to get a second evaluation of the tumor sample to confirm the diagnosis.  Mistakes are not common but are not rare. 

TIP  Try to set up the biopsy at a major research center.  When arranging your appointment or when requesting this of your oncologist, you might say that you want the extra tissue to be donated for lymphoma research.  This can lead to a priority appointment ... and it will increase the  chance that the most advanced diagnostic tests will be used on the tumor sample -- helping to inform your care and potentially helping to identify trials you can consider in the future.

The Pathology Report  

The completed report provides detailed information about the diagnosis or normalcy, such as

• Appearance (morphology), architecture, structure of the cells, such as small or large, cleaved, diffuse or nodular 
• Cell markers found by "staining," or immunohistochemistry tests: such as cd20, cd22, cd30... helping with identifying the cell of origin (CD stands for clusters of differentiation 
• Grade, the proportion of large to small cells
  
  Grade is often confused by patients with stage, which is done with imaging to show how widespread the lesions are in the body.  Stage is not diagnostic.  It shows areas of enlarged lymph nodes, but not the cause, which can be from inflammation.
• Gene rearrangements, such as bcl-2 or bcl-6, c-myc ...
• A diagnosis summary: the section where the pathologist gives a concise pathologic diagnosis. It includes the tumor type and cell of origin, or findings of normalcy (the sample is benign - not a cancer.

Other findings may be reported, such as:

Clonality: Are the lymphoid cells all alike?- clonal (monoclonal). Monoclonal supports the diagnosis of a lymphoid neoplasm although it is not considered an absolute indicator. 

Reactive hyperplasia:  indicating that the increase in the size of a lymph node is due to normal immune cells increasing in number in reaction to a pathogen (bacteria, or virus).

We urge you to ask for a copy of the pathology report for your records.

• It can help you to identify support groups with a focus on your type of lymphoma
• You will know what research studies and reports are related to your diagnosis.
• You will need it to seek advice (second opinions) from lymphoma experts.

We believe it's important to consult with experts and to become informed about your type of lymphoma, and all available treatments in order to receive optimal care. 

We recommend a second evaluation of the sample cells to confirm that the diagnosis is correct.  A second evaluation can be particularly important for the uncommon subtypes of lymphoma, or types that are inherently difficult to diagnose correctly.

Getting a second evaluation is a fairly routine procedure.  Studies show that a second review can sometimes change or refine the diagnosis. The slides are sent from one institution to another.  The report on the second evaluation is sent to your oncologist, who will discuss with you the findings.

 

An accurate diagnosis is critical to receiving the most appropriate treatment, as each lymphoma type can be treated very differently. Unfortunately an incorrect diagnosis, while not typical, is more common than we would like to think. 

Patient story: I want people to be aware of the importance of a second opinion. For almost eight years I have been treated for Mantle cell lymphoma. I was sent to a radiologist for evaluation of treatment and he questioned my diagnosis as Mantle cell is very aggressive and if I have had it for 8 years and I look so healthy, he said he has treated many patients with mantle cell I did not fit the diagnosis. He had previous biopsies sent to an entirely different hospital and have been diagnosed with low grade indolent lymphoma.

Information can ease your fear

The diagnosis of lymphoma is a blow that can take your breath away.  We hear the words "advanced" and "cancer," and will absorb little else our doctors say ... and fear the worst.  The stress of the diagnosis can be acute for the patient and for the caregivers. 

Time is needed to adjust and to learn.  Lymphoma can be a serious disease, however it's important to appreciate that it's typically very responsive to treatments even at advanced stages. 

... Hodgkin lymphoma, for example, has a high cure rate.  Many of the aggressive lymphomas, such as DLBCL, are cured, and the indolent types can be managed well as needed.  Recently, it was reported that the survival of patients with follicular lymphoma is often equivalent to persons of the same age without the diagnosis - the key milestone being event free survival (EFS) at 12 months after diagnosis or initial treatment. (ASH 2014) EFS means to be without any symptoms or medical issues related to lymphoma.

There can be, of course, no 100% certainty in life or in medicine. Outcomes will vary by the type of lymphoma and the unique clinical circumstances of the patient. That said, again and again, we observe that the anxiety level of patients will lessen with time, with experience, and with information.

Here is background that we trust will help you to feel more optimistic about how lymphoma is treated today ... noting that investigational targeted treatments are bound to improve substantially in the very near future!

Lymphoma is a treatable blood cell cancer that can be effectively treated at an advanced stage.  Lymphoma in the marrow is also reversible with treatment.

Lymphoma in the bone marrow (the nursery for blood cells) is not especially concerning because this is an expected place for normal lymphocytes to be found.

Many common aggressive types can be cured.  Treatment begins very soon after diagnosis with curative intent.  It can also be cured on relapse in many cases.

For the indolent types the approach and timing of treatment varies.  It is common to monitor or observe (watch and wait) an indolent lymphoma until there is a need to treat - when there are symptoms or evidence of steady progression. 

Dr. Bendandi notes: in this setting the likelihood of destroying most of the tumor with subsequent treatments is pretty much the same, irrespective of whether we treat right away (that has some side effects and risks) or carefully watch and wait (without side effects).

Sometimes (but not commonly), treatment of indolent lymphoma is never required. 

Treatments are improving rapidly with clinical research.  A reason we feel that clinical trials should be considered routinely.

A brief overview on the standard approaches to treating lymphoma: chemotherapy, Rituxan antibody, and radio-labeled antibodies (radioimmunotherapy).

The newly diagnosed can be initially fearful of chemotherapy, which are also called a cytotoxic agents. It’s important to appreciate that blood cell cancers are especially sensitive to this class of drug (and for similar reasons also to radiotherapy). These agents work by damaging the DNA of rapidly dividing cells – inducing the cells to self destruct -- similar to how a too much sun exposure causes our skin cells to self-destruct and peel.

Blood cells are inherently born to die (compared to say heart or lung cells). Thus, the doses of chemotherapy agents needed to have this effect is lower for lymphoma than for other types of cancers.  … Lymphoma arises from defective lymphocytes – a type of immune cell. Lymphocytes will expand in number in response to an infection and then die off when the cells receive signals from other cells that the task has been accomplished.

So lymphoma cells can be induced to die in different ways: by damaging them, by altering the signals they receive, or by targeting the defects that cause them to multiply too fast or persist too long.

The first types of cancer to be cured were the blood cell cancers treated with chemotherapy agents. Investigators looking for ways to treat childhood leukemias developed the concept by observing that the blood cell counts of soldiers drop when exposed to mustard gas, and that the counts would rebound later. They reasoned that at the right dose this kind of drug could treat blood cell cancers.

All treatments that are effective will have side effects, such as lowered normal blood cell counts. Antibodies can sometimes cause immune-mediated infusion reactions.

To be approved by the FDA as a therapy, the potential benefits of the drug must outweigh the known risks. This risk/benefit profile must be demonstrated in well controlled or large clinical trials that prospectively define the number of patients in the study and how the effects are measured. This provides a denominator, which is needed to estimate the rate of good and bad effects … such as for every 100 patients treated, 80 (80%) had a response that lasted … X months / years.

Your Individual Prognosis is not based on Group Statistics

The purpose of statistics is to find the average results and trends in LARGE groups.  These calculations are based on therapies used in the past.  Survival statistics should not be confused with an individual's prognosis, which is based on unique clinical factors, such as your age, type of lymphoma, where it is in the body, the underlying biology, and the response to therapies.  

Fortunately, for lymphoma a different class of therapy can be effective when the first treatment does not work optimally.  Cure and or achieving a durable remission can remain feasible and a realistic goal, even after multiple relapses.   Initially and sometimes at relapse the indolent types of lymphoma may not require any therapy, because they can grow very slowly without causing symptoms.

Misinformation on the Internet. 

If you are considering alternative practices please first review our comments that follow - explaining why you should be skeptical about such claims.

Life Style Changes can Help, but what about Alternative Medicine?

Overview:  Life style changes can help

Testimonials (why they can't be trusted)

Limitations of Cell Culture and Animal studies

Alternative Medicine?  | The Power, or Tyranny, of Positive Thinking?

Life style changes can improve your fitness, general health and quality of life.  These are sometime called complementary or integrative practices.  Here are suggestions with explanations further below.

• Take part in enjoyable forms of regular exercise ...
  to improve your fitness, to relieve stress, and to have fun 
• Adopt a diet that is delicious and promotes good health ...
• In times of stress, consider meditation, prayer, yoga, and aroma therapy
  
  For chronic anxiety and depression, please consult a professional.  Professionals can offer effective interventions to relieve chronic unproductive worry and depression. 
• Continue to live your life fully, such as by setting goals, doing self-actualizing work, and participating in social, artistic, or career activities that you find rewarding. 

Lymphoma survivors can and do often achieve their goals and a good quality of life.  The diagnosis can sometimes increase our appreciation of what is important in life.

Complementary medicine:
can life style changes help to improve outcomes?

Regular exercise is beneficial.  It can be safe to do even during treatment.  Regular exercise activities can improve your general health, fitness, reduce fatigue, and can improve your state of mind.  Unless done to excess, exercise has no major risks or side effects.  Maintaining and improving your fitness through exercise is also strongly associated with better survival.

Source:  MacMillan Cancer Support: "Move More: Physical activity the underrated 'wonder drug.'" http://bit.ly/1ygeKig

Exercise also appears to reduce the risk of neuropathy, a side effect of some kinds of lymphoma treatments lymphomation.org/side-effect-neuropathy

A healthful diet can also help to improve your fitness while decreasing the risks of developing secondary medical conditions.  Conversely, a poor diet can lead to health problems that can limit your ability to tolerate and recover from therapy. 

Can diet, herbs, or vitamins be used to treat lymphoma? 

It can be prudent to take vitamins (or choose foods more wisely) if you have a deficiency, based on credentialed tests.  A healthful diet can make a positive difference in some types of medical conditions (such as diabetes, heart disease, and high blood pressure) and it can help to improve our general health. 

Unfortunately, there is no clinical evidence to support the use of specific diets, herbs, or vitamins as a treatment for lymphoma - or plausible science supporting the theory. 

While deficiencies in vitamin D are associated with higher-risk aggressive lymphoma, it's not known if supplementation with this vitamin changes the prognosis.  Certainly, most people with low vitamin D levels never get lymphoma ... so it is not considered a causal risk factor.  It may be, for example that a faster growing, higher-risk lymphoma sequesters (uses up) this vitamin - in which case the deficiency is a result of the lymphoma, not a cause of it.  Scientists just don't know.

A relatively new understanding of  the role of epigenetics in cancer and cancer prevention has led to a wave of promotions of diet as treatments for cancer - or to help manage the disease.   Some foods may have epigenetic effects, but at this time the potential seems limited to cancer risk reduction for diets adopted over many years or decades.      

Observations and testimonials are not reliable

"For centuries doctors used leeches and lancets to relieve patients of their blood. They KNEW bloodletting worked. EVERYBODY said it did. When you had a fever and the doctor bled you, you got better.  EVERYONE knew of a friend or relative who had been at death’s door until bloodletting cured him. Doctors could recount thousands of successful cases."

Today we know that patients did well in spite of bloodletting, a practice based on primitive notions about the nature of diseases - attributed to bad elements in the blood.  The lesson from history is that observations are not reliable as evidence. 

In any observation or case report, even when from a reputable source, you can't tell what would have happened if something else – or nothing was done; you can't predict if others are likely to be helped or harmed by the same approach.

In modern clinical research the number of participants in a study is pre-specified and assessments are made in the same way. One approach is compared to another in late phase testing – the patients assigned to study groups randomly.  In all clinical studies you have a predefined denominator (the number of participants) that informs about the rate of good and bad effects.  These methods tell us what others (YOU) can expect … and how it compares to another established treatment. 

Testimonials have all of the limitations of observations  … with much less certainty about the facts: 

Did the person really have the medical condition?  Was it a false diagnosis of a cancer? 

You don't know how the outcome was measured: Was it that the patient felt better?  What tests were used to measure it?  Did the benefit last a week or 2 months?  

You can’t know what other medical treatments were given shortly before or after. Finally, people who provide testimonials and later die or get very sick cannot provide updates. 

The theories promoted to self-treat cancer are often borrowed from the literature... mainly from preclinical sources:  cell culture and animal experiments. 

Cell culture or in-vitro experiments:

• Cannot account for the doses needed to have a similar effect in the body
• Cannot not tell us if the compound is absorbed into the blood ... or if it is merely excreted
• Cannot provide information about the side effects of the compound when given at doses showing activity in the test tube.   Is it feasible or safe to take that much of it?
• Will not tell us if the herb you buy in a store (which is not regulated by the FDA) is free of contaminants. 
• Taking an herb at low dose may even do harm if the compounds in it have activity against a cancer.  Consider that tumor cells adapt to low or subclinical doses of treatment compounds of any kind.  
• Cancer cells put in a test tube are like fish taken out of water. Outside of the host environment they will die.
• Unlike bacteria, tumor cells are challenging to keep alive in any cell culture medium.  

... Animal experiments  (also only a starting point)

Such experiments cannot account for the profound differences between the mouse and human host environment.  The mouse immune system is different.  The tumor cell line is different.  Tumors implanted into a mouse are readily "cured" in the lab.

Further, the toxicities and activity of the compound in the mouse rarely predict good and bad effects in humans.  

So for complementary medicine, we recommend the avoidance of practices that have not been tested, unless, perhaps, when focused on improving your quality of life and fitness, such as meditation, yoga, and aroma therapy, exercise and maintaining a healthful diet.

If a vitamin or herb (used like a drug) is found to improve sleep or decrease fatigue in sufficiently powered and controlled clinical studies, then this practice will become part of regular medicine.  In such cases your doctor will be aware of the potential risks and benefits; the brand and dose will be understood and also the side effects.  

"Despite successful pre-clinical testing, 85% of early clinical trials for novel drugs fail; of those that survive through to phase III, only half become approved for clinical use [3]. The largest proportion of these failures occurs in trials for cancer drugs [4]. Furthermore, fewer than one in five cancer clinical trials find their way to the peer-reviewed literature, generally due to negative findings [5]. Although logistical and study design issues are often identified as the root cause of clinical trial failures, most futilities in fact originate from molecular mechanisms of the drug(s) tested [6]."