eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Lymphomas of the Head and Neck

Author: Kieron M Dunleavy, MD, Investigator/Attending Physician, National Cancer Institute
Coauthor(s): Erik Kass, MD, Chief, Department of Clinical Otolaryngology, Associates in Otolaryngology of Northern Virginia; Wyndham Wilson, MD, PhD, Senior Investigator, Division of Clinical Sciences, National Institutes of Health National Cancer Institute
Contributor Information and Disclosures

Updated: Dec 18, 2007

Introduction

Background

Otolaryngologists are frequently involved in the diagnosis of lymphoma. A quarter of all extranodal lymphomas occur in the head and neck, and 8% of findings on supraclavicular fine-needle aspirate biopsy yield a diagnosis of lymphoma. In white populations, lymphoma is a more common cause of cervical lymphadenopathy than metastatic disease. Lymphoma is the second most common primary malignancy occurring in the head and neck and importantly, the incidence of aggressive non-Hodgkin lymphoma has risen steadily over recent decades.

Pathophysiology

Although a variety of histologic classification schemes have been used for lymphoma in the past, the World Health Organization (WHO) classification is currently used.

The WHO classification of lymphomas is as follows:

  • Hodgkin lymphoma (HL)
    • Nodular lymphocyte predominant
    • Classic
    • Nodular sclerosis classic
    • Mixed cellularity classic
    • Lymphocyte-rich classic
    • Lymphocyte-depleted classic
  • Non-Hodgkin lymphoma (NHL) - B-cell neoplasms
    • Precursor B-cell neoplasms
    • Precursor B lymphoblastic leukemia/lymphoma
    • Mature B-cell neoplasms
      • Chronic lymphocytic leukemia, small lymphocytic lymphoma
      • Lymphoplasmacytic lymphoma
      • Splenic marginal-zone lymphoma
      • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)
      • Nodal marginal-zone lymphoma
      • Follicular lymphoma
      • Mantle-cell lymphoma
      • Diffuse large B-cell lymphoma (DLBCL)
      • Mediastinal (thymic) large B-cell lymphoma
      • Intravascular large B-cell lymphoma
      • Primary effusion lymphoma
      • Burkitt lymphoma/leukemia
    • B-cell proliferations of uncertain malignant potential
      • Lymphomatoid granulomatosis
      • Posttransplantation lymphoproliferative disorder, polymorphic
  • NHL - T-cell and natural killer (NK)–cell neoplasms
    • Precursor T-cell neoplasms
      • Precursor T lymphoblastic leukemia or lymphoma
      • Blastic NK-cell lymphoma
    • Mature T- and NK-cell neoplasms
      • Adult T-cell leukemia or lymphoma
      • Extranodal NK- or T-cell lymphoma, nasal type
      • Enteropathy-type T cell lymphoma
      • Hepatosplenic T-cell lymphoma
      • Subcutaneous panniculitis-like T cell lymphoma
      • Mycosis fungoides
      • Sezary syndrome
      • Primary cutaneous anaplastic large cell lymphoma
      • Peripheral T cell lymphoma, unspecified
      • Angioimmunoblastic T cell lymphoma
      • Anaplastic large cell lymphoma

HL is characterized by the presence of Reed-Sternberg (RS) cells, and the subtype diagnosis depends on the cytoarchitectural milieu in which the RS cells or their variants are found. Nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-depleted subtypes are collectively termed classic HL. Nodular sclerosis is the most common subtype, especially in patients younger than 40 years, followed by mixed cellularity. Lymphocyte-predominant HL, more common in young men than in others, behaves more like a low-grade B-cell lymphoma than other tumors. In general, patients who are elderly, those who live in developing countries, and those infected with HIV are most likely to have widespread disease with systemic symptoms at diagnosis.

Approximately 85% of NHLs are B-cell lymphomas. The most common indolent NHL is follicular lymphoma, which is derived from germinal center B cells. Other indolent histologies are lymphoplasmacytoid lymphoma, which has characteristics of B cells differentiating toward plasma cells, and marginal-zone lymphoma derived from the memory B-cell compartment, which includes MALT lymphomas. DLBCL is the most common aggressive NHL. On the basis of messenger RNA microarrays, most cases have profiles that indicate an origin from a germinal center B cell or a postgerminal-center activated B cell. Mantle-cell lymphoma and Burkitt lymphoma are aggressive NHLs that have the characteristics of normal B cells residing in the mantle zone or in the germinal center of a lymphoid follicle, respectively.

Cutaneous T-cell lymphomas, such as mycosis fungoides, can be indolent. However, many T-cell NHLs are aggressive malignancies.

Frequency

United States

Lymphoma is the sixth most common cancer in the United States, with an annual incidence of 64,000 estimated cases. Approximately 88% of these cancers are NHLs. The incidence of NHL has doubled over the last 20 years because of the increase in AIDS-related lymphoma (ARL); an increase in the detection of lymphoma; and for other, poorly understood reasons.

International

The different histologic subtypes of NHL have various distributions and geographic predilections. The frequency of NK/T-cell lymphoma is increased in China, in Taiwan, in Southeast Asia and in parts of Africa where Burkitt lymphoma is endemic.

Mortality/Morbidity

For HL, overall 5-year survival rates in the United States are 83% for whites and 77% for African Americans. For NHL, the 5-year survival rate is 53% for whites and 42% for African Americans.

Race

HL and, to a lesser extent, NHL are more common in whites than in African Americans or Hispanics. Other races such as Asian/Pacific islanders or American Indians have the lowest incidence and mortality rates.

Sex

The incidence of both HL and NHL are higher in men than in women, especially among older patients.

Age

  • In the United States, HL has a bimodal age distribution, with a peak incidence in people aged 20-34 years and a second peak in whites aged 75-79 years and in African Americans aged 55-64 years. In Japan, the early peak is absent, and in some developing countries, the early peak shifts into childhood.
  • The mortality rate increases with age. For example, incidence and mortality rates for NHL increase with age. In addition, Burkitt lymphoma represents 40-50% of all pediatric lymphomas but is uncommon in adults without AIDS.
  • Lymphoblastic lymphoma most commonly affects men aged 20-40 years who have lymphadenopathy and/or a mediastinal mass.

Clinical

History

Lymphoma may be nodal or extranodal. Extranodal lymphoma is usually NHL and worsens the patient's prognosis. HL extends by means of contiguous nodal spread; therefore, it is often localized and frequently occurs in the mediastinum. NHL tends to spread hematogenously and is often systemic at diagnosis.

  • A nodal presentation of HL is typically with 1 or more small-to-medium, rubbery lymph nodes in the neck, which may wax or wane in size but grow over time.
    • Biopsy should be considered when a firm lymph node larger than 1 cm that is not associated with infection and that persists longer than 4 weeks.
    • In 2-5% of patients with HL, involved nodes can become painful after they drink alcoholic beverages.
  • NHL may manifest in the cervical region and lymphoid tissue of the Waldeyer ring. It appears as a mass in the oropharynx or nasopharynx.
    • Unilateral tonsillar enlargement is highly suggestive of malignancy.
    • Extranodal disease, such as primary lymphoma, of the oral cavity is less common than other findings; this disease usually arises in the tongue base.
    • In contrast to squamous cell carcinoma, NHL is bulky, fleshy, and nonulcerating.
  • Extranodal NK/T-cell lymphoma, nasal type (formerly called lethal midline granuloma), can manifest as an ulcerative destructive lesion of the nose, sinuses, and face.
    • This lesion is usually associated with Epstein-Barr virus and worsens the patient's prognosis compared with that of patients with B-cell lymphoma.
    • The disease often manifests with a nasal mass, epistaxis, and/or nasal obstruction. (See Image 5 for a video of a fiberoptic examination of an NK/T-cell lymphoma in the right nasal cavity and maxillary sinus.)
  • Lymphoma in the thyroid is more common than anaplastic carcinoma of the thyroid. It manifests as a neck swelling, hoarseness, dysphagia, or neck pressure/tenderness.
    • Advanced disease can cause facial edema and Horner syndrome.
    • Extranodal marginal-zone B-cell lymphoma of MALT lymphoma occurs in the head and neck, in the ocular adnexa, and in thyroid areas.
    • Patients with Sjögren syndrome are at increased risk for MALT lymphomas in the oral mucosa.
    • Lymphoma involving the base of the skull or CNS can cause cranial nerve palsies, facial pain, hearing loss, vertigo, proptosis, or visual symptoms.
  • Constitutional symptoms, designated B symptoms, may occur in up to one third of patients with lymphoma.
    • B symptoms include weight loss greater than 10% of the patient's previous body weight, temperatures higher than 38°C without evidence of infection, and/or drenching night sweats.
    • Symptoms such as bony pain, headaches, or GI discomfort may indicate generalized disease.
    • A persistent cough can be the presenting feature of mediastinal lymphadenopathy, as can chest pain, shortness of breath, or hypertrophic osteoarthropathy.
    • Pruritus, malaise, fatigue, and weakness are nonspecific symptoms that occur in 10% of patients.

Physical

Full otorhinolaryngologic and neck examination including fiberoptic examination, in addition to complete physical examination, is indicated.

  • Examine patients for painless or mildly tender peripheral adenopathy in cervical, axillary, inguinal, and femoral regions. Less typically, enlargement of epitrochlear nodes is associated with enlargement of the Waldeyer ring.
  • Superior vena cava (SVC) syndrome and pleural effusions may be due to a mediastinal mass.
  • Some patients with indolent NHLs may have large, asymptomatic abdominal masses.
    • Splenic or hepatic enlargement may be detected.
    • The endemic (African) form of Burkitt lymphoma manifests as a jaw or abdominal tumor that spreads to extranodal sites, but the nonendemic (American) form has an abdominal presentation with massive disease.

Causes

  • Incidence of HL is increased 10-fold in same-sex siblings and by as much as 100-fold in identical twins. This observation implies genetic factors in the etiology.
    • Chromosomal abnormalities are common in lymphomas.
    • Aneuploidy occurs in HL, and translocations and deletions mark NHL, such as the c-myc translocation of Burkitt lymphoma and the bcl-2 translocation found in most follicular lymphomas.
  • Infectious agents implicated in the pathogenesis of some lymphomas include Epstein-Barr virus, HIV-1 (aggressive NHL occurs in 10-30% of patients with AIDS), Helicobacter pylori, human t-cell lymphotropic virus-1 (HTLV-1), hepatitis B and C viruses, human herpes virus 8, Borrelia burgdorferi, Chlamydia psittaci, and Campylobacter jejuni.
  • Chronic inflammation increases the risk of lymphoma, such as a MALT lymphoma arising in the salivary gland in a patient with Sjögren syndrome.
    • Hashimoto disease increases a patient's risk of thyroid lymphoma, usually aggressive NHL, about 70-fold.
    • In general, patients with autoimmune diseases, such as rheumatoid arthritis, have an increased risk of lymphoma.
  • Immunosuppressive medications, for example those used following organ allotransplantation, increase the risk of Epstein-Barr virus–associated NHL. A percentage of these lymphomas regress spontaneously when the immunosuppressive medication is discontinued.
  • Farming, welding, and work in the lumber industry are associated with an increased risk of lymphoma.

More on Lymphomas of the Head and Neck

Overview: Lymphomas of the Head and Neck
Differential Diagnoses & Workup: Lymphomas of the Head and Neck
Treatment & Medication: Lymphomas of the Head and Neck
Follow-up: Lymphomas of the Head and Neck
Multimedia: Lymphomas of the Head and Neck
References
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Further Reading

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Keywords

lymphomas of the head and neck, Hodgkin lymphoma, Hodgkin's lymphoma, HL, non-Hodgkin lymphoma, non-Hodgkin's lymphoma, NHL, nonHodgkin lymphoma, B-cell lymphomas, Reed-Sternberg cells, RS cells

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Contributor Information and Disclosures

Author

Kieron M Dunleavy, MD, Investigator/Attending Physician, National Cancer Institute
Kieron M Dunleavy, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Erik Kass, MD, Chief, Department of Clinical Otolaryngology, Associates in Otolaryngology of Northern Virginia
Erik Kass, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Association for Cancer Research, American Medical Association, and American Rhinologic Society
Disclosure: Nothing to disclose.

Wyndham Wilson, MD, PhD, Senior Investigator, Division of Clinical Sciences, National Institutes of Health National Cancer Institute
Disclosure: Nothing to disclose.

Medical Editor

Daniel J Kelley, MD, Consulting Staff, Eastern Shore ENT and Allergy Associates and Peninsula Regional Medical Center
Daniel J Kelley, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Laryngological Rhinological and Otological Society, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Karen Hall Calhoun, MD, Professor, Department of Otolaryngology-Head and Neck Surgery, The Ohio State University
Karen Hall Calhoun, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Medical Association, American Rhinologic Society, Association for Research in Otolaryngology, Society of University Otolaryngologists-Head and Neck Surgeons, Southern Medical Association, Texas Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation unstricted gift unknown; Axis Three Corporation Ownership interest Consulting; Omni Biosciences Ownership interest Consulting; Sentegra Ownership interest Board membership; Syndicom Ownership interest Consulting; Oxlo  Consulting; Medvoy Ownership interest Management position

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