typical presentation of lymphoma

• ASH Foundation
• Log in or create an account
• Publications
• Diversity Equity and Inclusion
• Global Initiatives
• American Society of Hematology
• Blood Cancers
• Agenda for Nematology Research
• Precision Medicine
• Genome Editing and Gene Therapy
• Immunologic Treatment
• Research Support and Funding

About half of the blood cancers that occur each year are lymphomas, or cancers of the lymphatic system. This system - composed of lymph nodes in your neck, armpits, groin, chest, and abdomen - removes excess fluids from your body and produces immune cells. Abnormal lymphocytes, a type of white blood cell that fights infection, become lymphoma cells, which multiply and collect in your lymph nodes. Over time, these cancerous cells impair your immune system.

Lymphomas are divided into two categories: Hodgkin lymphoma and non-Hodgkin lymphoma. About 12 percent of people with lymphoma have Hodgkin lymphoma. Because of  breakthrough research , this once fatal diagnosis has been transformed into a curable condition. Most non-Hodgkin lymphomas are B-cell lymphomas, and either grow quickly (high-grade) or slowly (low-grade). There are over a dozen types of B-cell non-Hodgkin lymphomas. The rest are T-cell lymphomas, named after a different cancerous white blood cell, or lymphocyte. 

How Lymphoma Develops

Many lymphoma patients are able to lead active lives as they receive treatment for their symptoms and are monitored by their doctors.

Am I at Risk?

The exact causes of lymphoma remain unknown; however, the following factors increase your risk of developing the disease:

• Having an autoimmune disease
• Diet high in meats and fat
• Being exposed to certain pesticides

Symptoms of lymphoma include the following:

• Swollen lymph nodes in the neck, armpits, or groin
• Weakness and fatigue
• Weight loss
• Difficulty breathing or chest pain

How is Lymphoma Treated?

Your doctor will perform a lymph node biopsy to diagnose lymphoma. Additional tests are then conducted to determine the stage (extent) of the lymphoma including blood tests, bone marrow biopsies, and imaging tests, such as a CT scan or PET scan. Imaging tests show whether the lymphoma has spread to other parts of your body, like the spleen and lungs. Decisions about treatment are then determined by your doctor, who will consider your age, general health, and stage and type of lymphoma. Hodgkin lymphoma is one of the most curable types of cancer.

Treatment options include the following:

• Chemotherapy
• Chemotherapy and radiation that  directly targets the lymphoma
• Biological therapies, such as antibodies, directed at lymphoma cells
• Stem cell transplant

For some patients, participating in a  clinical trial  provides access to experimental therapies. If you are diagnosed with lymphoma, talk with your doctor about whether joining a clinical trial is right for you.

Is Lymphoma Preventable?

Because the cause of lymphoma remains unknown, there is no real way to prevent it. However, if you think you may be exhibiting signs of lymphoma, being aware of the risk factors and symptoms and talking with your doctor are critical to early diagnosis and treatment. It is especially important if you have a family history of lymphoma to look out for symptoms and share your family medical history with your doctor.

If you suspect that you have or are at risk for lymphoma, talk with your doctor about detection and treatment. Depending on your physical condition, genetics, and medical history, you may be referred to a hematologist, a doctor who specializes in blood conditions.

Lymphoma: A Patient's Journey

Where Can I Find More Information?

If you find that you are interested in learning more about blood diseases and disorders, here are a few other resources that may be of some help:

Results of Clinical Studies Published in  Blood

Search  Blood , the official journal of ASH, for the results of the latest blood research. While recent articles generally require a subscriber login, patients interested in viewing an access-controlled article in  Blood  may obtain a copy by e-mailing a request to the  Blood  Publishing Office .

Patient Groups

A list of Web links to patient groups and other organizations that provide information.

Hodgkin Lymphoma

• 📖 Geeky Medics OSCE Book
• ⚡ Geeky Medics Bundles
• ✨ 1300+ OSCE Stations
• ✅ OSCE Checklist PDF Booklet
• 🧠 UKMLA AKT Question Bank
• 💊 PSA Question Bank
• 💉 Clinical Skills App
• 🗂️ Flashcard Collections | OSCE , Medicine , Surgery , Anatomy
• 💬 SCA Cases for MRCGP

To be the first to know about our latest videos subscribe to our YouTube channel 🙌

Table of Contents

Suggest an improvement

• Hidden Post Title
• Hidden Post URL
• Hidden Post ID
• Type of issue * N/A Fix spelling/grammar issue Add or fix a link Add or fix an image Add more detail Improve the quality of the writing Fix a factual error
• Please provide as much detail as possible * You don't need to tell us which article this feedback relates to, as we automatically capture that information for you.
• Your Email (optional) This allows us to get in touch for more details if required.
• Which organ is responsible for pumping blood around the body? * Enter a five letter word in lowercase
• Name This field is for validation purposes and should be left unchanged.

Introduction

• Hodgkin lymphoma (HL) is a haematological malignancy that arises from B lymphocytes in the lymphatic system.

In the United Kingdom, 2,100 people are diagnosed each year, with a peak incidence in young adults aged 20 – 34 years and in older adults aged over 70 years.

Overall, the prognosis is good with 75% of patients with HL surviving for ten years or more.

Prognosis is better in the younger population than in the older population. Younger patients under the age of 40-years-old have a five-year survival rate of 95% whereas older patients over the age of 70-years-old have a five-year survival rate of less than 50%. 1,2

The lymphatic system is a network of tissues and organs that play a key role in the immune system. This network consists of lymph nodes, lymphatic vessels, lymphatic organs and lymphatic fluid. 3

Lymphatic fluid contains a high number of lymphocytes and it is the mutation of these cells inside lymphoid tissues that results in a lymphoma.

Hodgkin lymphoma occurs when B lymphocytes, derived from the germinal centres of lymphoid tissues, mutate and lead to the presence of large , multi-nucleated giant cells called ‘Reed-Sternberg’ cells and large , mono-nucleated cells called malignant ‘Hodgkin cells’. 4,5

Classification

There are two main types of Hodgkin lymphoma (HL), classical Hodgkin lymphoma (which accounts for 95% of HL cases) and nodular lymphocyte-predominant Hodgkin lymphoma (which accounts for 5% of HL cases).

Classical Hodgkin lymphoma (cHL) is further subclassified into four types.

Table 1 . Classical Hodgkin lymphoma sub-classification.

Nodular lymphocyte-predominant Hodgkin lymphoma is a more indolent disease with little in common with cHL. It is associated with a risk of transformation to a high grade (rapidly growing) non-Hodgkin lymphoma. 7

Risk factors

The following risk factors are associated with an increased likelihood of developing HL:

• Epstein-Barr virus (EBV): it is estimated that around 40% of Hodgkin lymphoma cases in the UK are related to EBV infection. However, most people who have glandular fever will not develop cancer as a result. 3
• Human immunodeficiency virus (HIV): it is estimated that the risk of developing Hodgkin lymphoma is 11 times higher than that of the general population
• Immunosuppression: immunosuppressant drugs and certain autoimmune conditions such as rheumatoid arthritis increase the risk of developing HL
• Previous history of non-Hodgkin lymphoma (NHL) 
• First-degree relative family history of Hodgkin lymphoma, non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukaemia (CLL)
• Cigarette smoking

Clinical features

The most common symptom of Hodgkin lymphoma (HL) is a painless , rubbery , enlarged lymph node/nodes, typically in the cervical or supraclavicular region. 7

Other typical symptoms of Hodgkin lymphoma include:

• B symptoms: fever >38°C, drenching night sweats and unintentional weight loss of >10% within the last 6 months. These symptoms affect 25% of patient with HL.
• Chest discomfort +/- cough or dyspnoea: a mediastinal mass is present in 80% of patients with HL and may cause these symptoms 8
• Abdominal discomfort or pain: if abdominal lymphatic organs such as the liver or spleen have been affected
• Alcohol-induced pain at nodal sites: this is a ‘classical’ textbook symptom of Hodgkin Lymphoma but not often seen

Clinical examination

All patients with suspected Hodkin lymphoma require a through lymphoreticular system examination . 

On examination, clinical findings in HL may include:

• Lymphadenopathy
• Hepatomegaly
• Splenomegaly
• Superior vena cava (SVC) syndrome: a mediastinal mass may cause SVC obstruction
• Paraneoplastic syndromes such as cerebellar degeneration, neuropathy or Guillain-Barré syndrome

Differential diagnoses

The clinical presentation of Hodgkin lymphoma is similar to several other conditions including:

• Infectious mononucleosis
• Non-Hodgkin lymphoma
• Acquired immunodeficiency syndrome (AIDS)
• Tuberculosis
• Sarcoidosis
• Toxoplasmosis

Investigations

Laboratory investigations.

Relevant laboratory investigations include:

• FBC: to investigate for leukaemia, infectious mononucleosis and other causes of lymphadenopathy
• U&Es: to provide a baseline measurement before treatment
• LFTs: reduced albumin levels are associated with a poorer prognosis
• LDH: increased levels are associated with a poorer prognosis
• ESR: increased levels are associated with a poorer prognosis
• Tests to exclude differential diagnoses: for example, Monospot® test for infectious mononucleosis, sputum culture for TB, viral screen including HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) tests

Relevant imaging investigations include:

• Chest X-ray: to assess for intrathoracic lymphadenopathy and mediastinal expansion
• Contrast-enhanced CT neck, chest, abdomen and pelvis: usually performed when a patient first presents and is sometimes used for staging.
• Positron emission tomography CT (PET-CT): now the gold-standard for staging in cHL , and is repeated during treatment to allow guided therapy according to response (aiming to minimise toxicity by reducing chemotherapy intensity when possible)

Specialist investigations

Lymph node excision biopsy is required for diagnosis and classification of HL type.

On light microscopy, the hallmark cell is the Reed-Sternberg cell which is a giant malignant multi-nucleated cell that is often referred to as being “owl-like”. A collection of non-malignant immune cells also surround the Reed-Sternberg cells.

Hodgkin cells are giant malignant mono-nucleated cells and tend to be present surrounding Reed-Sternberg cells. 5

Using immunocytochemistry , CD15 and CD30 antigens are positively expressed on Reed-Sternberg cells.

A bone marrow biopsy is less frequently used as PET/CT can detect marrow involvement. 7

Once Hodgkin lymphoma is diagnosed, the disease is staged to determine prognosis and guide treatment options. Staging is performing using the Ann Arbor staging system . 8

The following table is a summarised version of the staging criteria; any more detail is beyond the scope of undergraduate learning.

Table 2 . A summarised version of the Ann Arbor staging system.

Prior to treatment, patients usually undergo cardiac function testing, pulmonary function testing and reproductive counselling due to the potential side effects of chemotherapy and radiotherapy.

Due to the increased risk of opportunistic infections following chemotherapy, patients are also usually vaccinated with the following: 8

• Polyvalent pneumococcal vaccine
• Influenza vaccine
• Meningococcal group C conjugate vaccine
• Haemophilus influenzae type b vaccine

Initial therapy 8

Early-stage disease (stage IA, IB, IIA) is usually treated with one or more cycles of combination chemotherapy plus radiotherapy .

Advanced stage (stage IIB or above) is usually treated with a more intensive chemotherapy course; often without radiotherapy unless a particularly large mass is present.

The most commonly used chemotherapy combination regimes in Hodgkin lymphoma are:

• ABVD: Doxorubicin (used to be called A driamycin®), B leomycin, V inblastine and D acarbazine
• BEACOPP: B leomycin, E toposide, Doxorubicin ( A driamycin®), C yclophosphamide, Vincristine ( O ncovin®), P rocarbazine, P rednisolone

Relapsed disease 10

Regardless of stage, relapsed disease is usually treated with high dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT).

HDCT aims to eradicate all HL cancer cells , however, bone marrow stem cells are also destroyed during the process.

The re-transfusion of the patient’s own haematopoietic stem cells (salvaged prior to HDCT) aims to promote a quicker recovery of bone marrow function and reduce the duration period of profound immunosuppression in the patient.

The chemotherapeutic regime chosen for patients eligible for ASCT is based on individual patient factors.

If a patient cannot tolerate intensive HDCT and ASCT, then combination chemotherapy and radiotherapy is considered. A more intensive chemotherapy regimen than that used in the initial therapeutic plan is usually offered.

If a patient cannot tolerate the toxicities associated with more intensive regimens, palliative chemotherapy and/or radiotherapy is considered.

Blood transfusion

If a transfusion of blood products is required, patients with or treated for Hodgkin lymphoma (at any stage of the disease) must only receive irradiated blood products . This is a lifelong requirement .

Irradiated blood products are used to reduce the risk of transfusion-associated graft-versus-host disease .

Complications

Disease-related complications.

Hodgkin lymphoma causes immunosuppression . The clonal expansion of B lymphocytes are abnormal and do not function properly. Patients are at a particularly higher risk of infection if there is bone marrow involvement.

Treatment-related complications

Treatment-related complications may include:

• Neutropenia: due to the effect of the chemotherapy on the bone marrow. Antibiotics are urgently required if patients are suspected to be neutropenic and have symptoms of infection or pyrexia ( neutropenic sepsis ). Patients can also be given granulocyte colony-stimulating factor (G-CSF) to stimulate the production of neutrophils which may reduce the duration of chemotherapy-induced neutropenia and therefore reduce the incidence of associated sepsis.
• Secondary solid tumours: particularly in the lung, skin, breast and gastrointestinal tract 1
• Secondary leukaemias: especially acute myeloid leukaemia
• Subfertility: patients should be counselled prior to treatment
• Cardiovascular disease: secondary to adriamycin/doxorubicin
• Lung fibrosis: secondary to bleomycin and presents months to years after treatment
• Endocrine dysfunction
• Nausea and vomiting
• Hodgkin lymphoma is characterised by the presence of Reed-Sternberg cells which are derived from germinal centre B lymphocytes.
• The main risk factor for Hodgkin lymphoma is previous EBV infection.
• Hodgkin lymphoma classically presents with a painless , rubbery , enlarged lymph node +/- ’ B symptoms ’
• The diagnosis is made by lymph node biopsy. PET-CT is used for staging in cHL.
• Management of Hodgkin lymphoma is with combination chemotherapy (usually either ABVD or BEACOPP) plus radiotherapy in early-stage disease or a longer, more intensive course of chemotherapy in advanced-stage disease. High dose chemotherapy and autologous stem cell transplantation are considered in relapsed disease.
• Complications include immunosuppression, low blood cell counts, secondary cancers, lung fibrosis, cardiovascular disease and subfertility.
• Prognosis is good with a 75% ten-year survival rate.

Please click here to fill out the feedback form, which should take less than 1 minute of your time. Feedback is vital as it allows authors to improve their articles, leading to even better content on Geeky Medics!

Dr Alex Langridge

Speciality Haematology Trainee (ST7)

Founder of Buku Medicine,  a free app answering the commonest questions put to haematology, renal and endocrine specialties.

Dr Chris Jefferies

References  .

• World Health Organisation. Hodgkin Lymphoma (Adult). Published in 2014. Available from: [ LINK ]
• Cancer Research UK. Hodgkin lymphoma Incidence Statistics. Published in 2015. Available from: [ LINK ]
• Cancer Research UK. About Hodgkin lymphoma. Published in 2020. Available from: [ LINK ]
• Patient UK. Hodgkin’s Lymphoma . Published in 2019. Available from: [ LINK ]
• Küppers R et al. Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling. Journal of Clinical Investigation. Published in 2003. Available from: [ LINK ]
• Cancer Research UK. Diagram of the Lymphatic system. License: [Public Domain]. Available from: [ LINK ]
• Townsend W et al. Hodgkin’s Lymphoma in Adults. The Lancet. Published in 2012. Available from: [ LINK ]
• Follows G et al. Guidelines for the first-line management of classical Hodgkin lymphoma. British Journal of Haematology. Published in 2014. Available from: [ LINK ]
• National Cancer Institute. Image of Reed-Sternberg Cell. License: [Public Domain]. Available from: [ LINK ]
• Ansell SM et al. Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management. American Journal of Hematology. Published in 2012. Available from: [ LINK ]

Other pages

• Product Bundles 🎉
• Join the Team 🙌
• Institutional Licence 📚
• OSCE Station Creator Tool 🩺
• Create and Share Flashcards 🗂️
• OSCE Group Chat 💬
• Newsletter 📰
• Advertise With Us

Join the community

• Request A New Patient Appointment
• Doctor Directory
• Other Provider Directory
• Find a Location
• Your First Appointment With OHC
• New Patient Forms
• Who to Call For Symptoms
• List of Clinical Trials
• Clinical Trial Locations
• Frequently Asked Questions About Clinical Trials
• OHC Locations, Phone, Fax
• Patient Education
• Frequently Asked Questions
• Financial Help and Support
• Pharmacy Services
• Community Support Resources
• Patient Guide to Cancer Treatment
• Patient Guide to Radiation Treatment
• Patient Guide for Nutrition
• What Differentiates OHC?
• Patient Referral Form
• OHC Forms For Your Patient
• OHC Medical Records Forms
• OHC Patient Genetic Counseling Referral Form
• Oncology Liaison Visits & Support
• Treatments & Services
• Stories of Hope
• OHC Newsletters
• DAISY Award
• News Releases
• Our Clinical Team
• Our Leaders
• Certifications, Recognitions & Innovations
• Public Notice
• Refer a Patient
• Pay Your Bill

The Clinical Presentation of Lymphomas

From Miguel Islas-Ohlmayer, M.D.

April 20, 2015

Miguel Islas-Ohlmayer, M.D.

Lymphomas, blood cell tumors that usually originate in lymphatic tissues (and can spread to other organs), are among the most diverse and most curable of all malignancies. There are two major groups of lymphomas: About 90 percent are non-Hodgkin lymphomas (NHLs) and about 10 percent are Hodgkin lymphomas (HLs).

NON-HODGKIN LYMPHOMAS (NHLs) Let’s start with NHLs, malignant neoplasms derived from B cell progenitors, T cell progenitors, mature B cells, mature T cells, or (rarely) natural killer cells. NHLs are the seventh most common type of cancer in American men and the sixth most common in American women. The American Cancer Society estimates nearly 72,000 cases and 20,000 deaths in 2015.

Clinical Presentation

Most NHL patients are first seen by their PCPs because they are showing signs of lymphadenopathy, although the enlarged nodes are usually painless. Here’s what your patients might present with:

• Aggressive NHLs usually present acutely or subacutely with a rapidly growing mass, systemic B symptoms (fever, night sweats, weight loss), and/or elevated levels of serum lactate. Treatment in these cases should be treated promptly to manage symptoms, slow or revert progression, and optimize survival.
• Indolent lymphomas often present only with slow-growing lymphadenopathy, hepatomegaly, splenomegaly, or cytopenias.
• Less commons presentations include skin rash, pruritus, hypersensitivity to insect stings and bites, generalized fatigue, malaise, fever of unknown origins, ascites, and effusions.
• Patients with primary GI track lymphoma may present with anorexia, weight loss, nausea and vomiting, chronic pain, abdominal fullness, early satiety, symptoms of visceral obstruction, or even acute perforation and GI hemorrhage.
• Patients with primary CNS lymphoma may have headache, lethargy, facial neurologic symptoms, seizures, paralysis, spinal cord compression or lymphomatous meningitis.

Risk Factors:

• Getting older is a strong risk factor for lymphoma overall, with most cases occurring in people in their 60s or older
• The risk of NHL is higher in men than in women, but there are certain types of non-Hodgkin lymphoma that are more common in women
• NHL in the United States is more common in Caucasians than African Americans or Asians
• Inordinate contact with chemicals such as benzene, and certain herbicides and insecticides
• Inordinate radiation exposure
• History of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren disease, and celiac sprue disease
• History of infections that directly transform lymphocytes such as T-cell leukemia/lymphoma virus (HTLV-1) and the Epstein-Barr virus (EBV)
• History of therapy with immunosuppressant drugs used in organ transplants, autoimmune disease, and HIV
• Inherited immune disorders such as hypogammaglobulinemia and Wiskott-Aldrich syndrome

HODGKIN LYMPHOMAS (HLs)

There are two major types of Hodgkin lymphomas: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Both are marked by the presence of HLs of the Reed-Sternberg cell. Note that this type of cell also can be found in reactive lymphadenopathy (such as infectious mononucleosis) and more rarely in other types of non-Hodgkin lymphomas. Both are marked by the presence of Reed-Sternberg cells.

According to the National Cancer Institute, the five-year survival rate (2004-2010) is 85.3 percent. And the number of deaths has been declining. Clinical Presentation:

Because there are no widely recommended screening tests for Hodgkin lymphomas, you will need to pay attention to your patient’s risk factors in combination with these clinical presentations:

• Asymptomatic lymphadenopathy, above the diaphragm 80% of time but also found under the arm or in the groin
• Intermittent fever is observed in approximately 35% of cases; infrequently, the classic Pel-Ebstein fever is observed (high fever for 1-2 weeks, followed by an afebrile period of 1-2 weeks)
• Chest pain, cough, shortness of breath, or a combination of those may be present due to a large mediastinal mass or lung involvement
• Patients may present with pruritus
• Pain at sites of nodal disease, precipitated by drinking alcohol, occurs in fewer than 10% of patients but is specific for Hodgkin lymphoma
• Back or bone pain may rarely occur
• A family history is also helpful; in particular, nodular sclerosis Hodgkin lymphoma (NSHL) has a strong genetic component and has often previously been diagnosed in the family
• History of infectious mononucleosis caused by Epstein Barr virus (EBV)
• Occurs slightly more often in men than women
• Most common with young adults (peaking at about 20) and older adults (peaking at about 65); and those in the United States, Canada, and Northern Europe
• History of younger siblings with the disease (but only by 5% per the American Cancer Society), and especially so with identical twins
• People from higher socioeconomic backgrounds (though the correlation is still unclear)
• People infected with HIV
• Lymphoma is widely diverse group of diseases that originate in lymphatic tissues
• Because the symptoms caused by lymphomas are often the same as those from infections, patient history, risk factors, and clinical presentation need to be viewed in total
• Presentation most often includes asymptomatic lymphadenopathy, usually found in the neck (above the diaphragm)
• Precise diagnosis and classification requires evaluation of lymph node tissue obtained via adequately sized biopsy
• Hodgkin lymphomas (HLs) and non-Hodgkin lymphomas (NHLs) are curable in the majority of patients

Miguel Islas-Ohlmayer, M.D. , is a hematologist and blood and marrow transplant physician. Board certified in internal medicine and hematology, his main interests include hematologic malignancies as well as blood and marrow stem cell transplantation. Dr. Islas-Ohlmayer practices at our OHC Kenwood office and is a clinician at the Blood Cancer Center at The Jewish Hospital-Mercy Health. The Blood Cancer Center, powered by OHC physicians, is a recent recipient of The Joint Commission’s Gold Seal of Approval for Blood & Marrow Transplants .

Leave a Reply Cancel reply

Your email address will not be published. Required fields are marked *

Low-Dose Radiation Therapy is an Effective Treatment for Osteoarthritis Pain

July 29, 2024

Managing pain with osteoarthritis can be a challenge. Some patients may have difficulty finding relief from typical pain

OHC Patient Saved By A Stranger Across the World

July 25, 2024

Aplastic Anemia (AA), a subtype of anemia, is a severe condition in which a person’s bone marrow cannot make enough

• Find a Doctor
• Clinical Trials
• Patient Resources
• For Medical Professionals
• Request an Appointment

Oncology Hematology Care, Inc.

Corporate Office

5053 Wooster Road

Cincinnati, OH 45226

1-800-710-4674 toll free

513-762-2483 fax

© 2015-2024 Oncology Hematology Care, Inc.

All Rights Reserved.

Privacy Policy

Lymphomas: pathogenesis, clinical features and diagnosis

Lymphomas are some of the most common cancers in the UK, with a wide variation in disease progression and prognosis between subtypes.

Steve Gschmeissner / Science Photo Library

The lymphomas are a large group of blood cancers with many subtypes. Hodgkin lymphoma has an incidence of 2.8 per 100,000 people per year in the UK, while non-Hodgkin lymphoma has an incidence of 15.5 per 100,000 people per year.

Both forms typically present with painless enlarged lymph nodes. Around a quarter of patients with Hodgkin lymphoma will also have night sweats, unexplained fever and weight loss. Diagnosis is made following a lymph node biopsy, a CT scan, and – in non-Hodgkin lymphoma – a bone marrow biopsy.

The lymphomas are a heterogenous group of blood cancers caused by the clonal proliferation of B or T lymphocytes. There are a large number of recognised subtypes of lymphoma, and it is beyond the scope of these articles to discuss each of them individually. Instead, the main focus will be on Hodgkin lymphoma and the most common forms of non-Hodgkin lymphoma.

Incidence and risk factors

Hodgkin lymphoma has an incidence in the UK of 2.8 per 100,000 people per year, which translates into just over 1,800 new cases per year [1] . The incidence of both Hodgkin lymphoma and non-Hodgkin lymphoma has increased by 11-15% in the past decade. This is most likely because of a combination of better diagnosis and reporting, the ageing population and an increase in the number of patients with a compromised immune system, such as those with HIV and AIDS.

Hodgkin lymphoma has a bimodal distribution, with an initial peak in young adults aged 20–24 years and a second peak between the ages of 70 years and 80 years, although it can occur at any age [1] .

The disease is slightly more common in men, with an incidence ratio of 1.2:1. The cause of Hodgkin lymphoma is not known, but it does have a strong association with being infected with Epstein-Barr virus, which is implicated in 45% of cases. It also occurs more commonly in patients who are immunocompromised; HIV infection is associated with an 11-fold increase in risk of Hodgkin lymphoma [1] , and patients who are receiving immunosuppressant therapy following an organ transplant or with autoimmune conditions such as rheumatoid arthritis and systemic lupus erythematosus are also at increased risk.

A small increase in risk of Hodgkin lymphoma has also been associated with tobacco exposure, having a first degree relative with the disease, and obesity. Rates of Hodgkin lymphoma in younger patients are lower for those with three or more siblings, suggesting that exposure to common childhood infections may somehow reduce the risk of developing the disease [2] .

Non-Hodgkin lymphoma has an incidence in the UK of 15.5 per 100,000 people per year, with almost 14,000 new cases reported in 2011 [1] . It is the sixth most common type of cancer in the UK, and accounts for about 4% of all cancers. It has a relatively good prognosis and, despite its high incidence, is the tenth most common cause of cancer death in the UK.

The incidence of non-Hodgkin lymphoma correlates closely with increasing age, and the majority of cases occur in patients aged 65 years or older. One exception to this rule is the relatively uncommon Burkitt’s lymphoma, in which almost 50% of cases occur in patients younger than 45 years.

There is a strong association between immunodeficiency, such as HIV infection, and risk of developing non-Hodgkin lymphoma. Recipients of organ transplantation who are receiving immunosuppressants such as ciclosporin or tacrolimus are at risk of developing post-transplant lymphoproliferative disease (PTLD), a proliferation of B cells caused by the Epstein-Barr virus that, if untreated, can progress to non-Hodgkin lymphoma.

Burkitt’s lymphoma is a highly aggressive form of non-Hodgkin lymphoma that, in its endemic form, is associated with malarial regions of equatorial Africa. In the UK, it accounts for about 2% of cases of lymphoma. It is more common in children and young adults.

The Epstein-Barr virus is implicated in the development of Burkitt’s lymphoma, although its overall importance as a risk factor is much less than for Hodgkin lymphoma.

Helicobacter pylori infection is strongly associated with mucosa-associated lymphoid tissue (MALT) lymphoma, a form of non-Hodgkin lymphoma that occurs in the stomach. H.pylori eradication regimens are the mainstay of treatment for this relatively rare subtype.

Other risk factors for non-Hodgkin lymphoma include hepatitis B and hepatitis C, working in rubber production and exposure to chemicals such as benzene and ethylene oxide. There is no proven association between smoking and an increased risk of non-Hodgkin lymphoma.

Classification

A variety of classification systems has been developed for lymphomas. The World Health Organization (WHO) classification, last updated in 2008, is currently the most widely used and recognises more than 50 different subtypes [3] .

Hodgkin lymphoma can itself be subdivided into two forms: classic Hodgkin lymphoma, which accounts for 95% of cases, and nodular lymphocyte predominant Hodgkin lymphoma.

The simplest way of classifying non-Hodgkin lymphomas is by the cell of origin. More than 90% originate in B-lymphocytes, with less than 10% being T-cell or NK cell lymphomas.

Clinically, it is often useful to separate non-Hodgkin lymphoma into aggressive (high grade) and indolent (low grade) forms (see ‘Aggressive and indolent lymphomas’).

Presentation

Hodgkin lymphoma commonly presents with painless swollen lymph nodes (lymphadenopathy), often affecting the cervical or supraclavicular nodes in the neck. About 25% of patients present with the three ‘B symptoms’: night sweats, unexplained fever and weight loss of more than 10% over six months. These symptoms are associated with a poorer prognosis [4] . Other presenting features include fatigue, itching and alcohol-induced pain.

Non-Hodgkin lymphoma also classically presents with painless enlarged lymph nodes. These are usually widespread in indolent lymphomas (such as follicular lymphoma), whereas progression is more rapid and often accompanied by B symptoms in aggressive lymphomas, such as diffuse large B-cell lymphoma.

In both Hodgkin lymphoma and non-Hodgkin lymphoma, patients are more likely to be unwell due to chemotherapy side effects than their cancer. A minority of patients will have lymphoma present in the bone marrow, which can lead to symptoms related to myelosuppression. These include fatigue, breathlessness, increased susceptibility to infections and unexpected bruising or bleeding.

Rarely, the location of the lymphoma mass may cause life-threatening complications such as spinal cord compression or obstruction of the superior vena cava. These are medical emergencies that require urgent treatment with chemotherapy or radiotherapy.

A lymph node or extranodal tissue biopsy is used to diagnose lymphoma, and immunohistochemistry is used to guide classification.

For example, classic Hodgkin lymphoma is defined by the presence of Reed-Sternberg (RS) cells, which stain positive for the antigens CD30 and CD15 located on the cell’s membranes. In contrast, lymphocyte predominant cells, which characteristically stain positive for the antigens CD20 and CD45, are expressed by cells in lymphocyte-predominant Hodgkin lymphoma [5] . These differences in surface antigen expression have important implications for treatment selection.

Determining the stage of the disease generally involves a contrast-enhanced computed tomography (CT) scan of the neck, chest, abdomen and pelvis and (in non-Hodgkin lymphoma) a bone marrow biopsy. Recently positron emission tomography (PET) scanning has become more widely used, both as part of diagnosis and as a means of accurately assessing response to treatment.

In addition, full blood count, lactic dehydrogenase, erythrocyte sedimentation rate, liver enzymes and urea and creatinine should be checked, and patients should be screened for hepatitis B, hepatitis C and HIV. Baseline cardiac function should be checked in patients who are going to receive anthracycline-based chemotherapy (see accompanying article).

Patients with either Hodgkin lymphoma or non-Hodgkin lymphoma are classified according to the Ann Arbor staging system (see ‘Ann Arbor staging system’).

For Hodgkin lymphoma, the following categories are then used to guide treatment [5] :

• Limited stage – Ann Arbor stage 1 or 2 disease without risk factors
• Intermediate stage – Ann Arbor stage 1 or 2 disease with risk factors (e.g., age >50 years, large mediastinal mass, elevated erythrocyte sedimentation rate)
• Advanced stage – Ann Arbor stage 3 or 4 disease

Around one third of patients with Hodgkin lymphoma will have advanced stage disease at diagnosis, and their prognosis can be calculated further (see ‘Hasenclever International Prognostic Score’) [6] .

Similar scoring systems can be used to guide treatment for some non-Hodgkin lymphomas, such as the international prognostic index (IPI) [7] for diffuse large B cell lymphoma, and the follicular lymphoma international prognostic index (FLIPI) [8] for follicular lymphoma. 

The prognosis for patients diagnosed with non-Hodgkin lymphoma in the UK has improved markedly in the past 30 years. The five-year survival rate is 63%, and half of all patients survive for at least ten years after diagnosis [1] .

However, there are marked variations in survival rates between subtypes of the disease. The most recent UK statistics indicate that 87% of patients with follicular lymphoma survive for at least five years, compared with 27% of patients with mantle cell lymphoma [1] . In general, patients with the rarer T-cell lymphomas have a poorer prognosis than patients with B-cell lymphomas.

Hodgkin lymphoma has a cure rate in the region of 80-90% [5] . The prognosis after intensive chemotherapy (with or without radiotherapy) has improved so much in recent decades that the focus has begun to move towards potentially less intensive approaches, with the aim of reducing long-term complications of therapy such as cardiac and pulmonary toxicity.

Nick Duncan MRPharmS MSc is principal pharmacist in haematology and oncology at University Hospitals Birmingham NHS Foundation Trust.

E: [email protected]

[1] Cancer Research UK. Cancer stats (Online). http://publications.cancerresearchuk.org/cancerstats (accessed 4 September 2014).

[2] Chang ET, Montgomery SM, Richiardi L et al. Number of siblings and risk of Hodgkin’s lymphoma. Cancer Epidemiology Biomarkers Prevention 2004;13:1236–1243.

[3] Swerdlow, Steven H. International Agency for Research on Cancer.  WHO classification of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours 2 (4th ed.). Geneva: World Health Organization, 2008. 

[4] Follows GA, Ardeshna KM, Barrington SF et al. Guidelines for the first line management of classical Hodgkin lymphoma. Br J Haem 2014;166:34–49.

[5] Eichenauer DA, Engert A, André M et al. Hodgkin’s lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014;25(suppl 3):iii70–iii75.

[6] Hasenclever D, Diehl V, Armitage JO  et al . A prognostic score for advanced Hodgkin’s disease. New Engl J Med 1998;339:1506–1514.

[7] The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. New Engl J Med 1993;329:987–994.

[8] Buske C, Hoster E, Dreyling M  et al. The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with respect to treatment outcome. Blood 2006;108:1504–1508.

You might also be interested in…

Combination treatment before surgery improves melanoma survival rates, study results show

Osimertinib treatment for advanced non-small cell lung cancer increases survival rates, study finds

Why we are helping patients with lung cancer symptoms self-refer for a chest X-ray

B-Cell Lymphoma Clinical Presentation

• Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
• Sections B-Cell Lymphoma
• Practice Essentials
• Classification
• Pathophysiology and Etiology
• Epidemiology
• Presentation
• Approach Considerations
• Laboratory Studies
• Other Tests
• Imaging Studies
• Histologic Findings
• Immunophenotypic Analysis
• Complications
• Consultations
• Risk Stratification
• Follicular Lymphoma
• Marginal Zone Lymphomas of MALT Type
• Mantle Cell Lymphoma
• Diffuse Large B-Cell Lymphoma
• Burkitt Lymphoma
• Primary Cutaneous B-Cell Lymphomas
• Medication Summary
• Hematopoietic Growth Factors
• Monoclonal Antibodies
• Corticosteroids
• Antineoplastic Agents
• Antineoplastics, Tyrosine Kinase Inhibitor
• Antineoplastics, PI3K Delta Inhibitors
• Antineoplastics, Angiogenesis inhibitor
• PD-1/PD-L1 Inhibitors
• Antineoplastics, Anti-CD19 Monoclonal Antibodies
• CAR T-cell Therapy
• Questions & Answers
• Media Gallery

History and Physical Examination

Lymphadenopathy is the most common manifestation of lymphoma. Lymphadenopathy may wax and wane. Spontaneous remissions have been documented, most commonly in patients with low-grade lymphomas.

Systemic symptoms (B symptoms) known to be associated with adverse prognosis include the following:

• Unexplained fevers
• Night sweats
• Weight loss

Organ-specific symptoms that may lead to identification of specific sites of involvement include the following:

• Shortness of breath, chest pain, cough
• Abdominal pain and distention
• Central nervous system (CNS) symptoms

Typical physical examination findings include the following:

• Pallor (suggesting anemia)
• Purpura, petechiae, or ecchymoses (suggesting thrombocytopenia)

Findings in patients with an advanced high-grade lymphoma may include the following:

• Tachycardia
• Respiratory distress

Examples of findings that might direct further investigations and subsequent therapy include the following:

• Pharyngeal involvement
• Thyroid mass
• Evidence of pleural effusion
• Abdominal mass
• Testicular mass
• Cutaneous lesions

Silkenstedt E, Salles G, Campo E, Dreyling M. B-cell non-Hodgkin lymphomas. Lancet . 2024 May 4. 403 (10438):1791-1807. [QxMD MEDLINE Link] .

Cancer Stat Facts: Non-Hodgkin Lymphoma. National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Available at https://seer.cancer.gov/statfacts/html/nhl.html . Accessed: May 29, 2024.

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues . 4th Edition, revised. Lyon, France: IARC; 2016.

Taborelli M, Polesel J, Montella M, Libra M, Tedeschi R, Battiston M, et al. Hepatitis B and C viruses and risk of non-Hodgkin lymphoma: a case-control study in Italy. Infect Agent Cancer . 2016. 11:27. [QxMD MEDLINE Link] .

Tanyildiz HG, Dincaslan H, Yavuz G, Unal E, Ikinciogulları A, Dogu F, et al. Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center. J Clin Immunol . 2016 Aug 4. [QxMD MEDLINE Link] .

Cancer Facts & Figures 2024. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf . Accessed: May 29, 2024.

Huang J, Chan SC, Lok V, Zhang L, Lucero-Prisno DE 3rd, Xu W, et al. Global burden, risk factors, and trends of non-Hodgkin lymphoma: A worldwide analysis of cancer registries. Cancer Med . 2024 Mar. 13 (5):e7056. [QxMD MEDLINE Link] .

Perry AM, Diebold J, Nathwani BN, MacLennan KA, Müller-Hermelink HK, Bast M, et al. Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project. Haematologica . 2016 Jun 27. [QxMD MEDLINE Link] .

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer . 2013 Apr. 49 (6):1374-403. [QxMD MEDLINE Link] .

International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med . 1993 Sep 30. 329(14):987-94. [QxMD MEDLINE Link] .

Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol . 2009 Sep 20. 27 (27):4555-62. [QxMD MEDLINE Link] . [Full Text] .

Solal-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood . 2004 Sep 1. 104(5):1258-65. [QxMD MEDLINE Link] . [Full Text] .

Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood . 2008 Jan 15. 111(2):558-65. [QxMD MEDLINE Link] . [Full Text] .

Choi WW, Weisenburger DD, Greiner TC, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res . 2009 Sep 1. 15(17):5494-502. [QxMD MEDLINE Link] .

American Joint Committee on Cancer, American Cancer Society, American College of Surgeons. Non-Hodgkin's lymphoma. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O'Sullivan B, Sobin LH, Yarbro JW, eds. AJCC Cancer Staging Manual . 5th ed. Philadelphia, Pa: Lippincott-Raven; 1997. 289-294.

Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol . 2014 Sep 20. 32 (27):3059-68. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] NCCN Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf . Version 2.2024 — April 30, 2024; Accessed: May 29, 2024.

Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J . 2014 Mar-Apr. 20 (2):119-22. [QxMD MEDLINE Link] .

FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm . October 18, 2017; Accessed: January 23, 2023.

Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol . 2019 Jan. 20 (1):31-42. [QxMD MEDLINE Link] . [Full Text] .

FDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma. U.S. Food and Drug Administration . 2018 May 03. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm606540.htm?utm_campaign=Oncology%205%2F1%2F2018_Kymriah&utm_medium=email&utm_source=Eloqua&elqTrackId=5578022d641d45d5a723adaf982a493c&elq=933c3d8ba491426680135d5ae119dcc6&elqaid=3339&elqat=1&e .

Schuster SJ, et al; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med . 2019 Jan 3. 380 (1):45-56. [QxMD MEDLINE Link] . [Full Text] .

Breyanzi (lisocabtagene maraleucel) [package insert]. Bothell, WA: Bristol Myers Squibb. 2/2021. Available at [Full Text] .

Enli Liu, David Marin, Pinaki Banerjee, Homer A Macapinlac, Philip Thompson, Rafet Basar, et al. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med . 2020 February 6. 2020; 382:545-553: [QxMD MEDLINE Link] .

FDA approves polatuzumab vedotin-piiq for diffuse large B-cell lymphoma. FDA . 2019 June 10. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-diffuse-large-b-cell-lymphoma .

Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol . 2020 Jan 10. 38 (2):155-165. [QxMD MEDLINE Link] .

Stephen J. Schuster, MD. Early-Phase Trial Shows Mosunetuzumab Induces Durable Complete Remissions in Patients With B-Cell Non-Hodgkin Lymphoma. ashclinicalnews.org . 2020 Jan 15. Available at https://www.ashclinicalnews.org/lymphomas-lymphoid-neoplasia/mosunetuzumab-induces-durable-complete-remissions-patients-b-cell-non-hodgkin-lymphoma/ .

Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program . 2009. 523-31. [QxMD MEDLINE Link] . [Full Text] .

Brice P, Bastion Y, Lepage E, Brousse N, Haïoun C, Moreau P, et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol . 1997 Mar. 15 (3):1110-7. [QxMD MEDLINE Link] .

[Guideline] Zucca E, Arcaini L, Buske C, Johnson PW, Ponzoni M, Raderer M, et al. Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol . 2020 Jan. 31 (1):17-29. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Dreyling M, Campo E, Hermine O, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol . 2017. 28 (suppl 4):iv62–iv71. [QxMD MEDLINE Link] . [Full Text] .

Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med . 2002 Jun 20. 346 (25):1937-47. [QxMD MEDLINE Link] .

[Guideline] Tilly H, Gomes da Silva M, Vitolo U, Jack A, Meignan M, Lopez-Guillermo A, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol . 2015 Sep. 26 Suppl 5:v116-25. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Senff NJ, Noordijk EM, Kim YH, Bagot M, Berti E, Cerroni L, et al. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood . 2008 Sep 1. 112 (5):1600-9. [QxMD MEDLINE Link] . [Full Text] .

Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood . 2005 May 15. 105 (10):3768-85. [QxMD MEDLINE Link] . [Full Text] .

Kim YH, Willemze R, Pimpinelli N, Whittaker S, Olsen EA, Ranki A, et al. TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC). Blood . 2007 Jul 15. 110 (2):479-84. [QxMD MEDLINE Link] . [Full Text] .

Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, et al. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood . 2017 Apr 20. 129 (16):2224-2232. [QxMD MEDLINE Link] . [Full Text] .

Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med . 2017 Dec 28. 377 (26):2531-2544. [QxMD MEDLINE Link] . [Full Text] .

Schuster S, et al. Primary Analysis of Juliet: A Global, Pivotal, Phase 2 Trial of CTL019 in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma. 59th American Society of Hematology Annual Meeting and Exposition. Abstract #577. Atlanta, GA. December 9-12, 2017.

Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, et al. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med . 2017 Dec 28. 377 (26):2545-2554. [QxMD MEDLINE Link] .

Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol . 2016 Jun 23. [QxMD MEDLINE Link] .

Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, et al. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer . 2016 Jun 28. [QxMD MEDLINE Link] .

Kansara R, Connors JM, Savage KJ, Gerrie AS, Scott DW, Slack GW, et al. Maintenance rituximab following induction R-CHOP chemotherapy in patients with composite or discordant, indolent and aggressive, B-cell non-Hodgkin lymphomas. Haematologica . 2016 Jun 16. [QxMD MEDLINE Link] . [Full Text] .

[Guideline] Dreyling M, Ghielmini M, Marcus R, Salles G, Vitolo U, Ladetto M, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol . 2014 Sep. 25 Suppl 3:iii76-82. [QxMD MEDLINE Link] . [Full Text] .

Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood . 2001 Jan 1. 97(1):101-6. [QxMD MEDLINE Link] .

Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol . 2005 Feb 20. 23 (6):1088-95. [QxMD MEDLINE Link] .

Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med . 2013 Oct 31. 369(18):1681-90. [QxMD MEDLINE Link] .

Hambley B, Caimi PF, William BM. Bortezomib for the treatment of mantle cell lymphoma: an update. Ther Adv Hematol . 2016 Aug. 7 (4):196-208. [QxMD MEDLINE Link] . [Full Text] .

Robak T, Huang H, Jin J, Zhu J, Liu T, Samoilova O, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med . 2015 Mar 5. 372 (10):944-53. [QxMD MEDLINE Link] .

Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood . 2014 Feb 6. 123 (6):837-42. [QxMD MEDLINE Link] .

Castillo JJ, Winer ES, Olszewski AJ. Population-based prognostic factors for survival in patients with Burkitt lymphoma: an analysis from the Surveillance, Epidemiology, and End Results database. Cancer . 2013 Oct 15. 119 (20):3672-9. [QxMD MEDLINE Link] .

WHO's cancer pain ladder for adults. World Health Organization. Available at https://www.who.int/cancer/palliative/painladder/en/ . Accessed: April 22, 2023.

National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer . 1982 May 15. 49 (10):2112-35. [QxMD MEDLINE Link] .

Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood . 1994 Sep 1. 84 (5):1361-92. [QxMD MEDLINE Link] . [Full Text] .

Rohatiner A, d'Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, et al. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol . 1994 May. 5 (5):397-400. [QxMD MEDLINE Link] .

Ruskoné-Fourmestraux A, Dragosics B, Morgner A, Wotherspoon A, De Jong D. Paris staging system for primary gastrointestinal lymphomas. Gut . 2003 Jun. 52 (6):912-3. [QxMD MEDLINE Link] . [Full Text] .

• Neoplastic follicles comprising cleaved cells (centrocytes) and larger cells with vesicular nuclei and prominent 2-3 nucleoli (centroblasts).
• Mantle cell lymphoma. Small lymphoid cells with oval to slightly irregular nuclei and clumped chromatin and rare admixed pink histiocytes.
• Diffuse large B-cell non-Hodgkin lymphoma. Large cells with abundant cytoplasm and large round-ovoid nuclei with thick nuclear membrane and multiple prominent nucleoli.
• Burkitt lymphoma. Normal architecture is entirely replaced by lymphoma cells and evenly dispersed macrophages, starry sky (250×).
• Burkitt lymphoma cells with round noncleaved nuclei and strongly basophilic cytoplasm (1000×).
• Compartmentalizing fibrosis and infiltrate of medium-sized to large lymphoid cells.
• Lymphoma cells show strong membranous positivity with CD20 indicative of B-cell origin.
• Table 1. Chromosomal Abnormalities in B-Cell Non-Hodgkin Lymphoma
• Table 2. Characteristic Immunophenotypes of Major Subtypes of Lymphoma
• Table 3. Lugano Modification of the Ann Arbor Staging System.
•   Table 4. Non-Hodgkin lymphoma staging.
• Table 3. International Society for Cutaneous Lymphoma/European Organization for Research and Treatment of Cancer tumor-node-metastasis classification for cutaneous B-cell lymphoma

Contributor Information and Disclosures

Mohammad Muhsin Chisti, MD, FACP Associate Professor of Medicine (Hematology and Oncology), Oakland University William Beaumont School of Medicine; Medical Director of Research, Karmanos Cancer Institute Mohammad Muhsin Chisti, MD, FACP is a member of the following medical societies: American College of Physicians , American Medical Association , American Society of Clinical Oncology , American Society of Hematology , Medical Society of the State of New York Disclosure: Nothing to disclose.

Haresh Kumar, MBBS Resident Physician, Department of Internal Medicine, St Joseph Mercy Oakland Hospital Disclosure: Nothing to disclose.

Sumeet K Yadav, MD, MBBS Resident Physician, Department of Internal Medicine, St Joseph Mercy Oakland Hospital Sumeet K Yadav, MD, MBBS is a member of the following medical societies: American College of Physicians , Asian Medical Students' Association International , Bangladesh Medical and Dental Council , European Society for Medical Oncology , Nepal Medical Association , We Care, Jahurul Islam Medical College and Hospital Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Received salary from Medscape for employment. for: Medscape.

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education , American Society of Clinical Oncology , American College of Clinical Pharmacology , American Federation for Medical Research , American Society of Hematology , New York Academy of Sciences Disclosure: Nothing to disclose.

Ajeet Gajra, MD Associate Professor of Medicine, Director of Hematology/Oncology Fellowship Program, State University of New York Upstate Medical University; Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Veterans Affairs Medical Center Ajeet Gajra, MD is a member of the following medical societies: American Association for Cancer Research , American Medical Association , American Society of Hematology Disclosure: Nothing to disclose.

Neerja Vajpayee, MD Associate Professor, Department of Pathology, State University of New York Upstate Medical University Neerja Vajpayee, MD is a member of the following medical societies: American Society of Hematology , College of American Pathologists , United States and Canadian Academy of Pathology Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Sara J Grethlein, MD, and Uzma Athar, MD, to the development and writing of the source article.

What would you like to print?

• Print this section
• Print the entire contents of
• Print the entire contents of article

• Diffuse Large B-Cell Lymphoma (Non-Hodgkin Lymphoma) Staging
• Non-Hodgkin Lymphoma Guidelines
• Cutaneous B-Cell Lymphoma
• B-Cell Lymphoma
• Diffuse Large B-Cell Lymphoma (DLBCL)
• Non-Hodgkin Lymphoma (NHL)
• Diffuse Large B-Cell Lymphoma (Non-Hodgkin Lymphoma) Treatment Protocols
• Mantle Cell Lymphoma: Drug Combo Improves PFS
• COVID Vaccine–Induced T-Cell Responses Help Compensate for B-Cell Deficiency
• FDA Approves Lymphir for R/R Cutaneous T-Cell Lymphoma

• Drug Interaction Checker
• Pill Identifier
• Calculators

• 20022007789-overviewDiseases & Conditions Diseases & Conditions Diffuse Large B-Cell Lymphoma (Non-Hodgkin Lymphoma) Staging

• 20022005945-overviewDiseases & Conditions Diseases & Conditions Diffuse Large B-Cell Lymphoma (Non-Hodgkin Lymphoma) Treatment Protocols

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Head Face Med

Clinical presentation and characteristics of lymphoma in the head and neck region

Katharina storck.

1 Department of ENT, Head and Neck Surgery, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany

Markus Brandstetter

Ulrich keller.

2 Third Department of Internal Medicine, Haematology and Oncology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany

Andreas Knopf

Associated data.

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

The study analyses clinical characteristics of histologically defined head and neck (H&N) lymphoma to raise the awareness of ENT specialists to the leading symptoms.

From 2003 to 2011, all patients with histologically defined H&N lymphoma from our clinic were evaluated.

This study identified 221 patients with H&N lymphoma comprising 193 non-Hodgkin lymphomas (NHL) and 28 Hodgkin lymphomas (HL). Among NHL there were 77 indolent (iNHL), 110 aggressive (aNHL), six highly aggressive NHL and further 28 HL. Patients with highly aggressive NHL and HL were significantly younger ( p  < 0.0001). Corresponding to the leading symptoms, we found nodal and extranodal involvement. NHL demonstrated manifestation in neck lymph nodes, tonsils, major salivary glands, sinonasal-system and hypopharynx/larynx. HL showed exclusive manifestation in lymph nodes of the neck and the tonsils ( p  < 0.0001). The mean time from first symptoms to diagnosis ranged from 1.5 ± 0.7 months in highly aggressive lymphoma to 7.5 ± 11.5 months in iNHL.

Conclusions

The variable clinical presentation of lymphoma is a challenge for the ENT specialist. Fast diagnosis is crucial for rapid treatment, especially in highly aggressive NHL like the Burkitt-lymphoma and HL. A standardized medical history, clinical examination and imaging evaluations paired with patient’s signs, symptoms and demographic knowledge might indicate lymphoma. Biopsies in the H&N region should always be immediately performed in suspicious findings.

Lymphomas are a heterogeneous group of malignant tumours of the haematopoietic system and are characterized by the aberrant proliferation of mature lymphoid cells or their precursors [ 1 ]. Lymphomas can be divided into two major entities: Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Over 20 different subtypes of NHL have been classified according to the specific subtype of lymphoid cells involved.

Several classifications have been developed over the years for lymphomas. The currently used classification is that of the World Health Organization (WHO) and is based on the principles of the Revised European-American Classification of Lymphoid Neoplasm (REAL) from 1994 [ 2 ]. The latest update of the classification was published in two reviews in Blood in 2016 [ 3 – 5 ]. The subtype of the lymphomas is defined based on the cell of origin: B-cell lymphomas, T-cell and natural killer-cell lymphomas (T/NK-NHL) and HL [ 6 , 7 ]. The two recent WHO classifications from 2008 and 2016 include and encompass (as previously stated in previous classifications) morphology, immunophenotype, genetic and clinical features in order to define “real” diseases [ 3 , 4 ]. HLs frequently involve lymph nodes of the neck and mediastinum, whereas extranodal sites account for only 5% of HLs for example in the tonsils. In contrast, approximately 30% of NHLs show heterogeneous extranodal manifestations, such as in the major salivary glands, paranasal sinuses, mandible, maxilla and Waldeyer’s ring (largely depending and often characteristic for the specific NHL subtype) [ 3 , 8 ]. Other than the gastrointestinal tract, the head and neck region is frequently involved as an extranodal site in NHL, affecting 11–33% of patients [ 9 ]. The clinical behaviour and manifestations of lymphomas in the head and neck region usually lack specific characteristics that would enable attribution to a specific lymphoma entity without biopsy and histological evidence. In particular, with regard to lymphomas having an aggressive course, immediate histological evidence is crucial for patient management, early treatment initiation and often for the outcome [ 10 , 11 ]. Available imaging techniques (ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET)) fail to distinguish HL from NHL and cannot differentiate their various subtypes, necessitating pathological diagnosis [ 8 ]. Sometimes, clinical parameters and the various sites within the head and neck can help to distinguish between the two categories as they each have predilections as mentioned above [ 3 ]. Typical symptoms can include an indolent lymphadenopathy (here, we concentrate on the cervical lymph nodes), fatigue, occasionally B-symptoms such as fever > 38 °C, night sweats and weight loss (> 10% within 6 month), susceptibility to infections and changes in the haemogram. Especially with respect to the differential blood count, iNHL presents cytopenia more often than aNHL but it does not lead to the diagnosis as a single parameter. In chronic lymphatic leukemia (CLL), for example, the frequency of lymphocytes in the differential blood count is elevated as a characteristic sign. Further symptoms of lymphoma might include anaemia, leucopenia/leucocytosis and thrombopenia, although specific serum and blood parameters might sometimes also suggest indolent vs aggressive lymphoma, e.g. elevated lactate dehydrogenase (LDH) in cases of highly proliferative disease or increased β2-microglobulin. The most important differential diagnosis for head and neck lymphadenopathy is infection or lymph-node metastasis from regional or distant primaries being affected by solid cancer.

Our retrospective study includes 221 patients who were suffering from NHL and HL and who were consecutively diagnosed in the Department of Otorhinolaryngology, Head and Neck surgery. Histologically confirmed lymphomas were classified according to the clinical system defined below. Thorough analysis of epidemiological data, leading symptomatology, clinical disease presentation and laboratory testing were carried out to identify clinical parameters in order to expedite diagnostic regimes/work-up.

Patients and methods

All patients presenting with head and neck symptoms that resulted in the histologically established diagnosis of lymphoma from January 2003 to December 2011 ( n  = 221) were included in this retrospective study. The study has been approved by the ethic committee of the Technical University of Munich (Permit Number: 493/17).

A standardized medical history was obtained from all patients: clinical examination, age at diagnosis, gender, location in the head and neck region, imaging evaluations (especially ultrasound), leading symptoms (B-symptoms; fever, night sweats, weight loss), time to diagnosis, known risk factors (HIV, EBV), histological findings and survival outcome (Munich cancer centre). All patients underwent clinical examination and a high-resolution B-mode ultrasound of the neck (S2000, tissue harmonic imaging, 9 MHz linear array, Siemens, Germany). Blood chemistry (including LDH and C-reactive protein (CRP)) and a complete blood count with a leucocyte differential count were undertaken. During diagnostic work-up (staging), all patients also underwent contrast CT-scans of the neck, chest, abdomen and pelvic cavity and bone marrow biopsy. If central nervous system involvement was suspected, staging also included contrast MR imaging of the brain and/or the spine.

Lymphomas were classified according to the lymphoma classification effective at the time: up until 2008, we used the Revised European American Lymphoma Classification (REAL) [ 2 ], and starting from 2008, we employed the WHO classification [ 3 , 4 ]. For practical purposes and because the observation period spanned two classifications, we refer here to lymphomas in two main categories, namely Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL). NHL were further clinically subgrouped into 1. indolent lymphoma (iNHL) (including follicular lymphomas and margional zone lymphomas), 2. aggressive lymphoma (aNHL) (e.g. DLBCL) and 3. highly aggressive lymphoma (Burkitt lymphoma and lymphoblastic lymphomas) (Fig. ​ (Fig.1 1 ).

Frequency of histologic subtypes within the iNHL, aNHL and highly aggressive lymphoma and HL

Statistical analyses were performed by using unpaired t-tests and one-way ANOVA testing (SPSS Inc., Chicago, IL). Post-hoc analysis was carried out with Tukey’s test. A p value of < 0.05 was considered statistically significant and a p value < 0.001 was defined as highly significant.

Epidemiology and characteristics of the head and neck cohort

A total of 221 patients were included in this study: 193 with NHL and 28 with HL. With respect to the clinical classification system, we included 77 indolent NHL (iNHL), 110 aggressive lymphomas (aNHL), 6 highly aggressive lymphomas and 28 HL (Fig. ​ (Fig.1). 1 ). The median age for indolent and for aggressive lymphoma was 70 years, for highly aggressive lymphoma 34 years and for HL 33 years. Patients with highly aggressive lymphoma and HL were significantly younger than their counterparts with less aggressive types ( p  < 0.0001; Table ​ Table1). 1 ). The study comprised 114 [52%] males and 107 [48%] females without differences between the groups (Table ​ (Table1 1 ).

Frequency of histologic types of head and neck lymphoma including also epidemiology, symptomatology, disease manifestations, localization and laboratory findings

aNHL Aggressive non-Hodgkin lymphoma, haNHL Highly aggressive non-Hodgkin lymphoma, HL Hodgkin lymphoma, iNHL Indolent non-Hodgkin lymphoma

The mean time from first symptoms to diagnosis ranged from 1.5 ± 0.7 months in highly aggressive lymphoma to 7.5 ± 11.5 months in indolent lymphoma. This difference was not statistically significant (Table ​ (Table1 1 ).

Independent from the classification the vast majority of lymphoma patients ( n  = 168) suffered from cervical masses as the leading symptom. Fifty-nine patients complained of odyno−/dysphagia. Globus pharyngis, dysphonia and dyspnea occurred infrequently. Occult lymphoma without clinical symptoms was diagnosed in five patients during sonographic procedure for another disease (Table ​ (Table1). 1 ). The distribution of leading symptoms differed significantly between the groups ( p  < 0.05, Table ​ Table1). 1 ). Whereas patients with highly aggressive lymphoma and HL usually presented with a cervical mass and/or odyno/dysphagia, patients with indolent and aggressive lymphoma demonstrated a broad variety of leading symptoms (Table ​ (Table1). 1 ). B-symptoms occurred in 28 (13%) patients (NHL, n  = 25; HL, n  = 3).

Disease manifestation

Corresponding to the diverse leading symptoms, we found a nodal and an extranodal involvement of the head and neck organs. NHL demonstrated manifestation in neck lymph nodes ( n  = 83), tonsils ( n  = 60), major salivary glands ( n  = 32), the sinonasal system ( n  = 6) and the hypopharynx/larynx ( n  = 7) whereas HL showed exclusive manifestation in neck lymph nodes ( n  = 27) and the tonsils ( n  = 1). Although highly aggressive NHL and HL exclusively originated in indolent neck lymph nodes and the tonsils, indolent and aggressive lymphomas showed a distinct disease heterotopia ( p  < 0.0001; Table ​ Table1). 1 ). In our study, extranodal head and neck manifestation occurred in 57% NHL and in 4% HL. NHL presented a unilateral localization in 84% of cases, and HLs were unilateral in 79% of cases. We found n  = 12 cases (20%) of NHL with bilaterally affected tonsils. Systemic involvement was seen in n  = 43 [56%] patients with iNHL, in n  = 75 [68%] patients with aNHL, in n = 6 [100%] patients with highly aggressive lymphoma, and in n  = 22 [79%] patients with HL.

Laboratory findings

Basic laboratory testing included blood counts, C-reactive protein (CRP) and lactate dehydrogenase (LDH). The level of leucocytes (normal range: 4.0–9.0 [G/l]) differed significantly between the groups ( p  < 0.05; Table ​ Table1). 1 ). However, all levels ranged within the norm. Patients with iNHL exhibited a leucocyte level of 11.8 ± 12.0 (mean ± SD), patients with aNHL 7.7 ± 3.6 and patients with HL 8.0 ± 3.0. In patients with highly aggressive lymphoma, the leucocyte level was significantly decreased at 4.5 ± 3.2. Similar results were seen in haemoglobin levels, which showed a normal level in all the groups, with the lowest level in highly aggressive lymphomas at 10.5 ± 6.1 (mean ± SD). Differences between haemoglobin levels were not statistically significant. CRP (normal range: < 0.5 [mg/dl]) was slightly elevated in all groups, with the highest level in HL at 3.30 ± 4.30 (mean ± SD). LDH levels (normal range: < 244 [U/l]) were elevated in aNHL at 278 ± 291[U/l] (mean ± SD) and in HL at 271 ± 121[U/l] (Table ​ (Table1 1 ).

Survival outcome

Available overall survival data for the previously defined subgroups are shown in Fig. ​ Fig.2 2 .

Overall survival data for the previously defined subgroups

Using the cox’s regression for forward selection, we also evaluated the survival rate depending on the laboratory findings. We could not find any significant differences in the survival rate depending on (pathological) laboratory findings (Fig. ​ (Fig.3 3 ).

Survival rate depending on the laboratory findings

Lymphoma is the third most common malignancy worldwide representing 3% of all malignant tumours. With 12% of all malignant tumours of the head and neck region, lymphomas are the third most frequent malignancy after squamous cell carcinoma (46%) and thyroid carcinoma (33%) [ 12 , 13 ] and should thus always be taken into consideration in cases of unknown cervical or oral masses. Misinterpretation of the clinical appearance and of the radiological findings (ultrasound, CT-scan, MRI) can lead to delay in diagnosis, delayed treatment initiation and impairment of the patient’s prognosis. In the current study, we have analysed clinical and epidemiological data of the entire lymphoma cohort diagnosed within an eight-year time frame at our ENT Department in order to bring to the attention of ENT specialists the specific clinical symptoms that allow the early diagnosis of lymphomas. In agreement with recent publications, we saw no differences in the gender distribution. Patients with HL (33 years) and highly aggressive lymphomas (34 years) were significantly younger than patients having other lymphoma subtypes (70 years) [ 14 , 15 ]. In our study, we found 193 NHL and 28 HL. Concordant with the present literature, diffuse large B-cell NHL (DLBCL) comprised the largest percentage of NHL in the head and neck region with 36.7% of cases [ 16 , 17 ]. Cervical lymphadenopathy (syn. nodal) is the most common site for both NHL and HL in the head and neck region. Differentiation from other causes of pathological lymph node enlargement caused by infectious diseases (CMV, EBV) or metastatic squamous cell carcinoma is crucial and often difficult and requires histopathological assessment. Certain differences, including the history of alcohol and / or tobacco use, the age of the patient, abnormalities in the clinical ENT examination, constitutional symptoms and systemic lymphadenopathy, may increase the probability of one versus the other. Associated mediastinal adenopathy is more common in HL and abdominal adenopathy in NHL [ 15 ]. In our series, we found n  = 110 (50%) patients presenting with cervical lymphadenopathy. Of these, 90 were unilateral and only 20 presented with a bilateral cervical lymphadenopathy. In HL, 22/27 were unilateral. An important aspect for ENT and maxillofacial specialists is the variety of extranodal sites. Taking all lymphomas together, we found 111 (50%) lymphomas in extranodal sites. In particular, NHL contributed to this high proportion. With n  = 110 of 193 NHL (57%), NHL presented an extranodal site in a surprisingly large number of cases. In the literature, 25–30% NHL occur in extranodal sites [ 18 ]. In HL, we found an extranodal site in just one case (palatine tonsils), whereas all other patients presented with cervical lymph nodes (96%). The literature also describes > 90% manifestations of HL occurring in the lymph nodes and only 1–4% involving extranodal areas [ 8 , 14 , 19 ]. The extranodal sites included in this study were the major salivary glands ( n  = 33), sinonasal system ( n  = 6), palatinal tonsils/nasopharynx ( n  = 60) and hypopharynx/larynx ( n  = 7). The literature also describes extranodal sites such as the palate, buccal mucosa, maxilla and mandible [ 8 , 20 ]. In our clinic, the patients with lymphomas in bone regions usually attend the Department of Maxillofacial Surgery; thus, patients with extranodal sites are partially preselected. The leading symptoms were correlated with the localization of the tumour mass, the majority of patients presenting with a cervical mass (76%) followed by odyno−/dysphagia, globus pharyngis, dysphonia and dyspnea.

Taking all patients together ( n  = 221), we found that only n  = 8 (13%) of the patients presented with constitutional symptoms or specific B-symptoms. Only n = 3 patients with HL suffered from B-symptoms. This low percentage agrees with the data in the literature [ 21 , 22 ]. Concentration on the presence or absence of B-symptoms might thus mislead the physician, as the rate of patients without such symptoms is high. The same also applies to results from blood and serum testing, as the majority of all of our patients had normal haemoglobin and leucocyte counts and only a few had slightly elevated levels of LDH and CRP. According to the WHO classification, two major subtypes of NHL (DLBCL 70–80% and Burkitt 7–20%) are related to HIV [ 23 ]. In our cohort, we found two HIV-positive patients. One of them was diagnosed with a nodal DLBCL and the other with nodal plasmablastic lymphoma (PBL), an aggressive and rare DLBCL subtype that is commonly found in patients with HIV [ 24 ].

Burkitt lymphoma (BL) is listed in the WHO’s classification of lymphoid tumours as an “aggressive B-cell non-Hodgkin’s lymphoma” characterized by a high degree of proliferation of malignant cells and deregulation of the MYC gene [ 25 ]. In our study, we found 5 cases of BL and all were male, as reported in the literature [ 20 ]; none of them were associated with HIV or EBV [ 26 ]. With a median age of 34 years, these patients were significantly younger ( p  < 0.0001) than patients suffering from iNHL or aNHL. Only 1.2% of BL are of extranodal origin in the head and neck [ 27 ]. We found three to be extranodal in the tonsils. The median time to diagnosis was 1.5 months. Despite its highly aggressive nature, BL is a curable lymphoma. Patients have a better prognosis when the diagnosis is established rapidly and if they present with a limited stage [ 28 ]. BL patients exhibited the lowest leucocyte and haemoglobin levels but the levels still ranged within the norm and the number of patients was too low to make a statistically valid statement. Patients with highly aggressive lymphomas and HL all presented with either a cervical mass as a sign of a nodal lymphoma or odynophagia / dysphagia, with the tonsils as the extranodal site in all cases, reflecting their admission to the ENT Department. These findings were highly significant compared with iNHL and aNHL aggressive lymphomas with a larger variety of localizations and leading symptoms. All six highly aggressive lymphomas showed a unilateral cervical mass but a systemic dissemination.

All Patients received standard therapies through the hematology department or associated hematologists/oncologist.

The focus of this report is to describe the different clinical presentations of lymphomas in the head and neck region and to raise awareness on the wide variety of symptoms. As we included all types of lymphoma that may manifest in the head and neck region, there is a large variety standard therapy approaches which sometimes were also adapted to comorbidity. Thus, the intend of this report was not to focus on this clearly important issue which is covered by numerous publications and results from prospective studies. Furthermore, treatment standards have evolved during the observation time of the patient groups described herein.

Concerning the survival outcome, we could see significant differences between the groups as expected. In the blood and serum testings we did not see any differences concerning the survival rate, which strengthens our assumption that we can not identify lymphomas in the head and neck region only by laboratory findings.

Lymphomas comprise 12% of all head and neck malignancies. The variable clinical presentation of lymphoma, in addition to the nodal involvement, is sometimes a challenge for the ENT specialist. A rapid diagnosis is crucial for early treatment initiation, especially in cases of BL and HL, which mostly affect younger patients. A standardized medical history, clinical examination and imaging evaluations (especially ultrasound) paired with patient’s signs, symptoms and demographic knowledge (e.g. age, gender, HIV, EBV) may lead to a correct diagnosis and accelerated the decision for a biopsy.

Tumours in the head and neck are easily accessible and a biopsy should immediately be performed following suspicious findings. In particular, for NHL with extranodal involvement in the head and neck occurring at a frequency of 20–30%, biopsy should always be part of the diagnosis in any head and neck lesion, including those in the oral cavity, major salivary glands, oropharynx, nasopharynx, paranasal sinus and larynx. Unilaterality, the absence of EBV or other acute viruses, the absence of an obvious tumour and a systemic involvement (if previously noted at the first presentation) should alert the ENT specialist to lymphomas, even in the absence of B-symptoms or blood disturbances.

Acknowledgments

This work was supported by the German Research Foundation (DFG) and the Technical University of Munich within the funding programme Open Access Publishing.

The corresponding author states no financial or other relationships with other people or organizations, which may lead to a conflict of interest.

Availability of data and materials

Authors’ contributions.

Conceived and designed the study: KS, AK, MB. Performed the study and analysed the data: KS, MB, UK, AK. Wrote the paper: KS. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The study has been approved by the ethic committee of the Technical University of Munich (Permit Number: 493/17).

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Katharina Storck, Phone: 0049-89-4140-2370, Email: moc.oohay@kcrots_anirahtak .

Markus Brandstetter, Phone: 0049-89-4140-2370, Email: [email protected] .

Ulrich Keller, Phone: 0049-89-4140-4111, Email: [email protected] .

Andreas Knopf, Phone: 0049-89-4140-2370, Email: [email protected] .

• Patient Care & Health Information
• Diseases & Conditions
• Lymphoma FAQs

Hematologist Stephen Ansell, M.D., answers the most frequently asked questions about lymphoma.

Well, many times we don't actually know. We do know what exactly happens in the cells. We can see that the cells undergo a genetic change. And as they do that, they may grow quicker than they should, and they may persist and not die off like they should. That causes them to slowly accumulate over time. But exactly what brought about that genetic change, we don't always know.

This is not a disease that's passed down in families, although families can be more susceptible. But we think there are some susceptibility genes that may put you at risk for being more likely to get lymphoma. That does, however, require something else to happen, often in the way of exposures to toxins or viruses or something else.

Well, I think it's important to recognize what the goals of treatment are. Low-grade lymphomas have an advantage in that they can take a very long time to cause any symptoms, and certainly a very long time to put the patient's health at risk. However, we do not have a curative treatment that will fix the cancer right away. So we want to weigh up the potential risks and side effects that come with treatment compared to, clearly, the risks and side effects that come from the cancer. So, if you have a cancer that is very low-grade, growing very slowly, giving you no symptoms, we would hold off on treatment and only initiate it when you truly need it.

Well, important to know that chemotherapy may have two components. Chemotherapy, or chemical drugs that are targeting the cancer, immunotherapy, or antibody treatments that are going after proteins that are on the outside of the cancer or lymphoma cells. The goal of chemotherapy is to kill quickly- growing cells, which is a good thing because lymphoma, many times, those cells are growing quickly. The challenge, however, is there are healthy cells that may also be growing quickly. Immunotherapy, as I mentioned, binds or attacks proteins on the outsides of cells. But some of the lymphoma cells and some of the normal cells have the same proteins. So those cells may be depleted, and your immune system may become a little bit more suppressed as one of the potential side effects of therapy.

Well, I really wish that was true. Unfortunately, that's not exactly correct. There isn't a treatment or exercise program that directly targets or goes after the lymphoma cells. Generally, however, what a healthy balanced diet and a good exercise program is doing is improving your general well-being, improving your immune system function, and allowing you to tolerate the chemotherapy and fight against the cancer to a greater degree. The good news is that many studies have shown that a healthy patient who's in good shape actually has a better outcome when receiving treatment for lymphoma. So that's a strong motivation for you to be healthy by eating well and exercising regularly.

Get as much information as you can. Partner with your physician, your nurse practitioner, your PA and other members of the team and ask questions. The goal moving forward is for you to have the best outcome possible. So that sharing of information between your team and you is critical to your outcome and the best results we could hope for.

Bone marrow exam

In a bone marrow aspiration, a healthcare professional uses a thin needle to remove a small amount of liquid bone marrow. It is usually taken from a spot in the back of the hipbone, also called the pelvis. A bone marrow biopsy is often done at the same time. This second procedure removes a small piece of bone tissue and the enclosed marrow.

Lymphoma diagnosis often begins with an exam that checks for swollen lymph nodes in the neck, underarm and groin. Other tests include imaging tests and removing some cells for testing. The type of tests used for diagnosis may depend on the lymphoma's location and your symptoms.

Physical Exam

A healthcare professional may start by asking about your symptoms. The health professional also may ask about your health history.

Next, the healthcare professional may feel and press on parts of your body to check for swelling or pain. To find swollen lymph nodes, the health professional may feel your neck, underarm and groin. Be sure to say if you have felt any lumps or pain.

A biopsy is a procedure to remove a sample of tissue for testing in a lab. For lymphoma, the biopsy typically involves removing one or more lymph nodes. The lymph nodes go to a lab for testing to look for cancer cells. Other special tests give more details about the cancer cells. Your healthcare team will use this information to make a treatment plan.

Imaging tests

Your healthcare team may recommend imaging tests to look for signs of lymphoma in other areas of your body. Tests may include CT, MRI and positron emission tomography scans, also called PET scans.

• Care at Mayo Clinic

Our caring team of Mayo Clinic experts can help you with your lymphoma-related health concerns Start Here

Many types of treatments exist for lymphoma. Treatments include radiation, chemotherapy, immunotherapy, targeted therapy and bone marrow transplant, also called stem cell transplant. Sometimes, a combination of treatments is used. The treatment that's best for you will depend on the kind of lymphoma that you have.

Treatment might not need to start right away

Treatment for lymphoma doesn't always need to start right away. Some types of lymphoma grow very slowly. You and your healthcare professional may decide to wait and have treatment if the cancer starts to cause symptoms.

If you don't have treatment, you'll have regular appointments with your healthcare professional to monitor symptoms.

Chemotherapy

Chemotherapy treats cancer with strong medicines. Most chemotherapy medicines are given through a vein. Some come in pill form. Two or more of these medicines together are often used to treat lymphoma.

Immunotherapy

Immunotherapy for cancer is a treatment with medicine that helps the body's immune system to kill cancer cells. The immune system fights off diseases by attacking germs and other cells that shouldn't be in the body. Cancer cells survive by hiding from the immune system. Immunotherapy helps the immune system cells find and kill the cancer cells. It can be given for different types of lymphoma.

Targeted therapy

Targeted therapy for cancer is a treatment that uses medicines that attack specific chemicals in the cancer cells. By blocking these chemicals, targeted treatments can cause cancer cells to die. Your lymphoma cells might be tested to see if targeted therapy will help you.

Radiation therapy

Radiation therapy treats cancer with powerful energy beams. The energy comes from X-rays, protons or other sources. During radiation therapy, you lie on a table while a machine moves around you. The machine directs radiation to precise points in your body.

CAR-T cell therapy

Chimeric antigen receptor (CAR)-T cell therapy, also called CAR-T cell therapy, trains your immune system cells to fight lymphoma. This treatment begins with removing some white blood cells, including T cells, from your blood. The cells are sent to a lab. In the lab, the cells are treated to recognize the lymphoma cells. The cells are then put back into your body. They then can find and destroy the lymphoma cells.

More Information

Lymphoma care at Mayo Clinic

There is a problem with information submitted for this request. Review/update the information highlighted below and resubmit the form.

Get Mayo Clinic cancer expertise delivered to your inbox.

Subscribe for free and receive an in-depth guide to coping with cancer, plus helpful information on how to get a second opinion. You can unsubscribe at any time. Click here for an email preview.

Error Select a topic

Error Email field is required

Error Include a valid email address

To provide you with the most relevant and helpful information, and understand which information is beneficial, we may combine your email and website usage information with other information we have about you. If you are a Mayo Clinic patient, this could include protected health information. If we combine this information with your protected health information, we will treat all of that information as protected health information and will only use or disclose that information as set forth in our notice of privacy practices. You may opt-out of email communications at any time by clicking on the unsubscribe link in the e-mail.

Thank you for subscribing

Your in-depth coping with cancer guide will be in your inbox shortly. You will also receive emails from Mayo Clinic on the latest about cancer news, research, and care.

If you don’t receive our email within 5 minutes, check your SPAM folder, then contact us at [email protected] .

Sorry something went wrong with your subscription

Please, try again in a couple of minutes

Clinical trials

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

Alternative medicine

No alternative medicines have been found to treat lymphoma. But integrative medicine may help you cope with the stress of a cancer diagnosis and the side effects of cancer treatment.

Talk to your healthcare professional about your options, such as:

• Acupuncture.
• Art therapy.
• Meditation.
• Music therapy.
• Physical activity.
• Relaxation exercises.

Coping and support

A lymphoma diagnosis can be overwhelming. With time you'll find ways to cope with the stress and uncertainty that often comes with a lymphoma diagnosis. Until then, you may find that it helps to:

Follow us on Twitter

Learn about lymphoma.

If you'd like to know more about your lymphoma, ask your healthcare professional for the details of your cancer. Ask about the type and your prognosis. Ask for good sources of up-to-date information on your treatment options. Knowing more about your cancer and your options may help you feel more confident when making treatment decisions.

Keep your friends and family close

Your friends and family can be emotional support and provide the practical support you'll need, too, such as helping take care of your house if you're in the hospital.

Find someone to talk with

Find a good listener with whom you can talk about your hopes and fears. This may be a friend or a family member. The concern and understanding of a counselor, medical social worker, clergy member or cancer support group also may be helpful. Ask your healthcare professional about support groups in your area. You also might contact a cancer organization such as the National Cancer Institute or the Leukemia & Lymphoma Society.

Preparing for your appointment

Make an appointment with a doctor or other healthcare professional if you have any symptoms that worry you. If your healthcare professional suspects that you have lymphoma, that person may refer you to a doctor who specializes in diseases that affect the blood cells. This kind of doctor is called a hematologist.

Appointments can be brief, and there's a lot to discuss. It's a good idea to be prepared. Here's how to help get ready and what to expect:

What you can do

• Be aware of any pre-appointment restrictions. When you make the appointment, ask if you need to do anything in advance, like restrict your diet.
• Write down any symptoms you're experiencing, even any that may seem unrelated to why you scheduled the appointment.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medications, vitamins or supplements you're taking.
• Consider taking a family member or friend along. Sometimes it can be difficult to remember all the information provided during an appointment. Someone who accompanies you may remember something that you missed or forgot.
• Write down questions to ask your healthcare professional.

Your time with your healthcare professional is limited, so preparing a list of questions can help you make the most of your time together. List your questions from most important to least important in case time runs out. For lymphoma, some basic questions to ask include:

• Do I have lymphoma?
• What type of lymphoma do I have?
• What stage is my lymphoma?
• Is my lymphoma aggressive or slow growing?
• Will I need more tests?
• Will I need treatment?
• What are my treatment options?
• What are the potential side effects of each treatment?
• How will treatment affect my daily life? Can I continue working?
• How long will treatment last?
• Is there one treatment that you feel is best for me?
• If you had a friend or loved one in my situation, what advice would you give that person?
• Should I see a lymphoma specialist? What will that cost, and will my insurance cover it?
• Do you have brochures or other printed material that I can take with me? What websites do you recommend?

Ask any other questions that come to mind during your appointment.

What to expect from your doctor

Your healthcare professional is likely to ask you several questions. Being ready to answer them may allow more time to cover other points you want to address. Your healthcare professional may ask:

• When did you first experience symptoms?
• Are your symptoms continuous or occasional?
• How severe are your symptoms?
• What, if anything, helps improve your symptoms?
• What, if anything, worsens your symptoms?
• Has anyone in your family had cancer, including lymphoma?
• Have you or has anyone in your family had immune system conditions?
• Have you or your family been exposed to toxins?
• Lymphoma – Non-Hodgkin. Cancer.Net. https:www.cancer.net/cancer-types/41246/view-all. Accessed Dec. 18, 2023.
• Lymphoma – Patient version. National Cancer Institute. https://www.cancer.gov/types/lymphoma. Accessed Dec. 18, 2023.
• What causes non-Hodgkin lymphoma? American Cancer Society. https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/causes-risks-prevention/what-causes.html. Accessed Dec. 21, 2023.
• Elsevier Point of Care. Clinical Overview: Hodgkin lymphoma. https://www.clinicalkey.com. Accessed Dec. 21, 2023.
• Freedman A, et al. Clinical presentation and initial evaluation of non-Hodgkin lymphoma. https://www.uptodate.com/contents/search. Accessed Jan. 30, 2024.
• Lymphoma – Non-Hodgkin: Diagnosis. https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/diagnosis. Accessed Dec. 22, 2023.
• Non-Hodgkin lymphoma treatment (PDQ) – Patient version. National Cancer Institute. https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq. Accessed Jan. 1, 2024.
• Brondfield S, et al. Developing a community for patients with cancer through longer-term art therapy. Oncology Practice. 2020; doi:10.1200/OP.20.00419.
• Distress management. National Comprehensive Cancer Network. https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1431. Accessed Jan. 3, 2024.
• Coping with cancer. Cancer.Net. https://www.cancer.net/coping-with-cancer. Accessed Jan. 4, 2024.
• Robetorye R, et al. Incorporation of digital gene expression profiling for cell-of-origin determination (Lymph2Cx Testing) into the routine work-up of diffuse large B-Cell lymphoma. Journal of Hematopathology. 2019; doi:10.1007/s12308-019-00344-0.
• Laurent C, et al. Impact of expert pathologic review of lymphoma diagnosis: Study of patients from the French Lymphopath Network. Journal of Clinical Oncology. 2017; doi:10.1200/JCO.2016.71.2083.
• Member institutions. Alliance for Clinical Trials in Oncology. https://www.allianceforclinicaltrialsinoncology.org/main/public/standard.xhtml?path=%2FPublic%2FInstitutions. Accessed April 14, 2024.
• Membership institution lists. NRG Oncology. https://www.nrgoncology.org/About-Us/Membership/Member-Institution-Lists. Accessed April 14, 2024.
• Lymph node clusters
• What is lymphoma? An expert explains

News from Mayo Clinic

• Mayo Clinic Minute: How precise diagnosis of lymphoma offers patients best treatment options Jan. 26, 2024, 05:00 p.m. CDT
• Mayo Clinic Q and A: What is lymphoma? Nov. 03, 2022, 01:04 p.m. CDT

Products & Services

• A Book: Living Medicine
• Symptoms & causes
• Diagnosis & treatment
• Doctors & departments

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.

• Opportunities

Mayo Clinic Press

Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press .

• Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence
• The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book
• Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance
• FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment
• Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book

Help transform healthcare

Your donation can make a difference in the future of healthcare. Give now to support Mayo Clinic's research.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• My Bibliography
• Collections
• Citation manager

Save citation to file

Email citation, add to collections.

• Create a new collection
• Add to an existing collection

Add to My Bibliography

Your saved search, create a file for external citation management software, your rss feed.

• Search in PubMed
• Search in NLM Catalog
• Add to Search

Presentation, staging and diagnosis of lymphoma: a clinical perspective

Affiliation.

• 1 Department of Physiology, Fatima Jinnah Dental College, Karachi, Pakistan. [email protected]
• PMID: 19999217

Background: Due to lack of awareness among health professionals, lymphoma is often misdiagnosed. This study was done to evaluate the clinical features and histopathologic subtypes of lymphoma.

Methods: Sixty diagnosed cases of lymphoma were selected (aged 12-65 years) from medical units of Civil Hospital Karachi, during 1993 to 1998. Clinical history, physical examination and basic laboratory investigations including imaging procedures were done in all the patients. The diagnosis of lymphoma was based on histology, following the International Working Formulation classification system. This included lymph node biopsy and in some cases, biopsy of the bone marrow. The Ann Arbor Staging Classification was used to classify the extent of disease.

Results: Out of 60 cases of lymphoma, 81.6% (49 cases) were diagnosed as non-Hodgkin's lymphoma and 18.3% (11 cases) as Hodgkin's disease, with an overall male predominance. Both categories exhibited a bimodal age distribution. Lymphadenopathy was the commonest presenting features in both the types of lymphomas; however, patients with Hodgkin's disease had a prominence of 'B' symptoms, whereas abdominal signs and symptoms were more common in non-Hodgkin's lymphoma. On histopathology, majority of non-Hodgkin's lymphomas (91.8%) showed a diffuse pattern, while mixed cellularity was the commonest type seen in Hodgkin's disease (81.8%).

Conclusion: Non-Hodgkin's lymphoma was 4 times more common than Hodgkin's disease. The vast clinical spectrum of lymphoma sometimes delays its diagnosis, leading to its eventual presentation in late stages. A general awareness is hence required among the health professionals regarding its varied clinical presentations.

PubMed Disclaimer

Similar articles

• Malignant lymphoma in western Ethiopia. Getachew A. Getachew A. East Afr Med J. 2001 Aug;78(8):402-4. East Afr Med J. 2001. PMID: 11921560
• Primary non-hodgkin's lymphoma of bone: experience of a decade. Qureshi A, Ali A, Riaz N, Pervez S. Qureshi A, et al. Indian J Pathol Microbiol. 2010 Apr-Jun;53(2):267-70. doi: 10.4103/0377-4929.64340. Indian J Pathol Microbiol. 2010. PMID: 20551530
• Lymphoma in adult Nigerians. Adelusola KA, Adeniji KA, Somotun GO. Adelusola KA, et al. West Afr J Med. 2001 Apr-Jun;20(2):123-6. West Afr J Med. 2001. PMID: 11768010
• Primary colorectal lymphomas. Wong MT, Eu KW. Wong MT, et al. Colorectal Dis. 2006 Sep;8(7):586-91. doi: 10.1111/j.1463-1318.2006.01021.x. Colorectal Dis. 2006. PMID: 16919111 Review.
• Hodgkin's lymphoma in adults--clinical features. Jose BO, Koerner P, Spanos WJ Jr, Paris KJ, Silverman CL, Yashar C, Carrascosa LB. Jose BO, et al. J Ky Med Assoc. 2005 Jan;103(1):15-7. J Ky Med Assoc. 2005. PMID: 15682982 Review.
• Autologous Hematopoietic Stem Cell Transplantation-10 Years of Data From a Developing Country. Ali N, Adil SN, Shaikh MU. Ali N, et al. Stem Cells Transl Med. 2015 Aug;4(8):873-7. doi: 10.5966/sctm.2015-0015. Epub 2015 Jun 1. Stem Cells Transl Med. 2015. PMID: 26032748 Free PMC article.
• Search in MeSH

LinkOut - more resources

• MedlinePlus Health Information
• Citation Manager

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Information

• Author Services

Initiatives

You are accessing a machine-readable page. In order to be human-readable, please install an RSS reader.

All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess .

Feature papers represent the most advanced research with significant potential for high impact in the field. A Feature Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for future research directions and describes possible research applications.

Feature papers are submitted upon individual invitation or recommendation by the scientific editors and must receive positive feedback from the reviewers.

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Original Submission Date Received: .

• Active Journals
• Find a Journal
• Proceedings Series
• For Authors
• For Reviewers
• For Editors
• For Librarians
• For Publishers
• For Societies
• For Conference Organizers
• Open Access Policy
• Institutional Open Access Program
• Special Issues Guidelines
• Editorial Process
• Research and Publication Ethics
• Article Processing Charges
• Testimonials
• Preprints.org
• SciProfiles
• Encyclopedia

Article Menu

• Subscribe SciFeed
• Author Biographies
• Google Scholar
• on Google Scholar
• Table of Contents

Find support for a specific problem in the support section of our website.

Please let us know what you think of our products and services.

Visit our dedicated information section to learn more about MDPI.

JSmol Viewer

Primary cauda equina lymphoma mimicking meningioma.

1. Introduction

2.1. clinical neurological presentation, 2.2. imaging findings and additional diagnostics, 2.3. operative findings and histopathology, 2.4. postoperative recovery, 2.5. management in the infectious diseases department and follow-up, 2.6. subsequent oncological treatment, 2.7. long-term follow-up and prognosis, 3. materials and methods.

• Intravenous chemotherapy: administered to 27% of patients, aimed at systemic disease control;
• Radiotherapy: applied in 44% of cases, targeting the tumor localized within the spinal canal;
• Surgical intervention: cytoreductive surgeries performed in 11% of cases, aimed at decompressing neural structures and alleviating symptoms.

5. Discussion

5.1. clinical presentation, 5.2. diagnostic approaches, 5.3. differential diagnosis, 5.4. histopathological examination and diagnosis, 5.5. management and prognosis, 5.6. comparative analysis, 5.7. limitations, 6. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

• Mally, R.; Sharma, M.; Khan, S.; Velho, V. Primary lumbo-sacral spinal epidural non-hodgkin’s lymphoma: A case report and review of literature. Asian Spine J. 2011 , 5 , 192–195. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Moussaly, E.; Nazha, B.; Zaarour, M.; Atallah, J.P. Primary Non-Hodgkin’s Lymphoma of the Spine: A Case Report and Liter-ature Review. World J. Oncol. 2015 , 6 , 459–463. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Kuhlman, J.J.; Moustafa, M.A.; Gupta, V.; Jiang, L.; Tun, H.W. Primary Cauda Equina Lymphoma Treated with CNS-Centric Approach: A Case Report and Literature Review. J. Blood Med. 2021 , 12 , 645–652. [ Google Scholar ] [ CrossRef ]
• Nakamizo, T.; Inoue, H.; Udaka, F.; Oda, M.; Kawai, M.; Uemura, K.; Takahashi, M.; Nishinaka, K.; Sawada, H.; Kameyama, M.; et al. Magnetic Resonance Imaging of Primary Spinal Intramedullary Lymphoma. J. Neuroimaging 2002 , 12 , 183–186. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Mauney, M.; Sciotto, C.G. Primary malignant lymphoma of the cauda equina. Am. J. Surg. Pathol. 1983 , 7 , 185–190. [ Google Scholar ] [ CrossRef ]
• Toner, G.C.; Holmes, R.; Sinclair, R.A.; Tang, S.; Schwarz, M.A. Central nervous system lymphoma: Primary lumbar nerve root infiltration. Acta Haematol. 1989 , 81 , 44–47. [ Google Scholar ] [ CrossRef ]
• Klein, P.; Zientek, G.; VandenBerg, S.R.; Lothman, E. Primary CNS lymphoma: Lymphomatous meningitis presenting as a cauda equina lesion in an AIDS patient. Can. J. Neurol. Sci. J. Can. Sci. Neurol. 1990 , 17 , 329–331. [ Google Scholar ] [ CrossRef ]
• Giobbia, M.; Carniato, A.; Scotton, P.G.; Vaglia, A.; Marchiori, G.C. Primary EBV-associated cauda equina lymphoma. J. Neurol. 1999 , 246 , 739–740. [ Google Scholar ] [ CrossRef ]
• Zagami, A.; Granot, R. Non-Hodgkin’s lymphoma involving the cauda equina and ocular cranial nerves: Case reports and literature review. J. Clin. Neurosci. 2003 , 10 , 696–699. [ Google Scholar ] [ CrossRef ]
• Tajima, Y.; Sudo, K.; Matumoto, A. Malignant lymphoma originating in the cauda equina mimicking the inflammatory poly-radiculoneuropathy. Intern. Med. 2007 , 46 , 1029–1032. [ Google Scholar ] [ CrossRef ]
• Khong, P.; Pitham, T.; Owler, B. Isolated neurolymphomatosis of the cauda equina and filum terminale: Case report. Spine 2008 , 33 , 807–811. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Beitzke, M.; Enzinger, C.; Beitzke, D.; Neureiter, D.; Ladurner, G.; Fazekas, F. Primary leptomeningeal lymphoma of the cauda equina: A rare cause of radiculopathy. J. Neurol. 2010 , 257 , 1734–1737. [ Google Scholar ] [ CrossRef ]
• Teo, M.K.; Mathieson, C.; Carruthers, R.; Stewart, W.; Alakandy, L. Cauda equina lymphoma—A rare presentation of primary central nervous system lymphoma: Case report and literature review. Br. J. Neurosurg. 2012 , 26 , 868–871. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Cugati, G.; Singh, M.; Symss, N.; Pande, A.; Vasudevan, M.; Ramamurthi, R. Primary spinal intradural extramedullary lymphoma causing cauda equina syndrome. J. Craniovertebral Junction Spine 2012 , 3 , 58–61. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Iwasaki, M.; Hida, K.; Yano, S.; Aoyama, T.; Kaneko, S.; Iwasaki, Y. Primary cauda equina lymphoma treated with high-dose metho-trexate. Neurol. Med. Chir. 2012 , 52 , 679–683. [ Google Scholar ] [ CrossRef ]
• Nishida, H.; Hori, M.; Obara, K. Primary B-cell lymphoma of the cauda equina, successfully treated with high-dose methotrexate plus high-dose cytarabine: A case report with MRI findings. Neurol. Sci. 2011 , 33 , 403–407. [ Google Scholar ] [ CrossRef ]
• Nakashima, H.; Imagama, S.; Ito, Z.; Ando, K.; Kobayashi, K.; Ukai, J.; Muramoto, A.; Shinjyo, R.; Matsumoto, T.; Yamauchi, I.; et al. Primary cauda equina lymphoma: Case report and literature review. Nagoya J. Med. Sci. 2014 , 76 , 349–354. [ Google Scholar ]
• Broen, M.; Draak, T.; Riedl, R.G.; Weber, W.E.J. Diffuse large B-cell lymphoma of the cauda equina. BMJ Case Rep. 2014 , 2014 , 1–5. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Shin, H.K.; Oh, S.K.; Woo, C.G.; Huh, J.R.; Suh, C.W.; Jeon, S.R. Cauda equina lymphoma mimicking non-neoplastic hypertrophic neu-ropathy of the cauda equina: A case report. Br. J. Neurosurg. 2016 , 30 , 678–680. [ Google Scholar ] [ CrossRef ]
• Belcastro, V.; Bellcocchi, S.; Patriarca, C.; Gini, G.; Piola, M.; Barca, S.; Arnaboldi, M. Cauda equina syndrome due to large B-cell lymphoma: A case report. Neurol. Sci. 2016 , 37 , 825–827. [ Google Scholar ] [ CrossRef ]
• Suzuki, K.; Yasuda, T.; Hiraiwa, T.; Kanamori, M.; Kimura, T.; Kawaguchi, Y. Primary cauda equina lymphoma diagnosed by nerve biopsy: A case report and literature review. Oncol. Lett. 2018 , 16 , 623–631. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Sutherland, T.; Yap, K.; Liew, E.; Tartaglia, C.; Pang, M.; Trost, N. Primary central nervous system lymphoma in immunocompetent patients: A retrospective review of MRI features. J. Med. Imaging Radiat. Oncol. 2012 , 56 , 295–301. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Mapelli, P.; Vanoli, E.; Picchio, M.; Gianolli, L. Spinal cord involvement secondary to non-Hodgkin’s lymphoma identified by 18F-FDG PET/CT. Rev. Espanola Med. Nucl. Imagen Mol. 2013 , 32 , 125. [ Google Scholar ] [ CrossRef ]
• Feng, L.; Chen, D.; Zhou, H.; Shen, C.; Wang, H.; Sun, X.; Liang, X.; Chen, L. Spinal primary central nervous system lymphoma: Case report and literature review. J. Clin. Neurosci. 2018 , 50 , 16–19. [ Google Scholar ] [ CrossRef ]
• Benz, R.; Viecelli, A.; Taverna, C.; Schelosky, L. Paroxysmal non-kinesigenic dyskinesia due to spinal cord infiltration of low-grade B cell non-Hodgkin’s lymphoma. Ann. Hematol. 2012 , 91 , 463–465. [ Google Scholar ] [ CrossRef ]
• Guzzetta, M.; Drexler, S.; Buonocore, B.; Donovan, V. Primary CNS T-cell lymphoma of the spinal cord: Case Report and literature review. Lab. Med. 2015 , 46 , 159–163. [ Google Scholar ] [ CrossRef ]
• Rao, A.; Griffiths, R.; Arnaoutakis, K. Paralyzed by a rare cause: An unusual case of metastatic diffuse large B cell lymphoma of the intramedullary spinal cord. Ann. Hematol. 2013 , 93 , 337–338. [ Google Scholar ] [ CrossRef ]

Click here to enlarge figure

Share and Cite

Lapolla, P.; Maiola, V.; Familiari, P.; Tomei, G.; Gangemi, D.; Ienzi, S.; Arcese, R.; Palmieri, M.; Relucenti, M.; Mingoli, A.; et al. Primary Cauda Equina Lymphoma Mimicking Meningioma. J. Clin. Med. 2024 , 13 , 4959. https://doi.org/10.3390/jcm13164959

Lapolla P, Maiola V, Familiari P, Tomei G, Gangemi D, Ienzi S, Arcese R, Palmieri M, Relucenti M, Mingoli A, et al. Primary Cauda Equina Lymphoma Mimicking Meningioma. Journal of Clinical Medicine . 2024; 13(16):4959. https://doi.org/10.3390/jcm13164959

Lapolla, Pierfrancesco, Vincenza Maiola, Pietro Familiari, Gabriella Tomei, Dominella Gangemi, Sara Ienzi, Roberto Arcese, Mauro Palmieri, Michela Relucenti, Andrea Mingoli, and et al. 2024. "Primary Cauda Equina Lymphoma Mimicking Meningioma" Journal of Clinical Medicine 13, no. 16: 4959. https://doi.org/10.3390/jcm13164959

Article Metrics

Article access statistics, further information, mdpi initiatives, follow mdpi.

Subscribe to receive issue release notifications and newsletters from MDPI journals