Lymphomas of the Head and Neck

Updated: Jul 17, 2017
  • Author: Kieron M Dunleavy, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Overview

Practice Essentials

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. Lymphoma is the second most common primary malignancy occurring in the head and neck. See the image below.

CT scan of a patient with a natural killer (NK)/T- CT scan of a patient with a natural killer (NK)/T-cell lymphoma of the right nasal cavity and maxillary sinus.

Signs and symptoms

Lymphoma may be nodal or extranodal. Common symptoms include the following:

  • Nodal presentation of Hodgkin lymphoma (HL) – 1 or more small-to-medium, rubbery lymph nodes in the neck, which may wax or wane in size but grow over time
  • Non-Hodgkin lymphoma (NHL) – Mass in the oropharynx or nasopharynx
  • Extranodal natural killer (NK)/T-cell lymphoma, nasal type – Ulcerative destructive lesion of the nose, sinuses, and face
  • Lymphoma in the thyroid – Neck swelling, hoarseness, dysphagia, or neck pressure/tenderness
  • Constitutional symptoms (B symptoms) – These may occur in up to one third of patients with lymphoma

Full otorhinolaryngologic and neck examination including fiberoptic examination, in addition to complete physical examination, is indicated. Physical findings that may be noted include the following:

  • Painless or mildly tender peripheral adenopathy in cervical, axillary, inguinal, and femoral regions
  • Superior vena cava syndrome and pleural effusions (from a mediastinal mass)
  • In some patients with indolent NHL, a large, asymptomatic abdominal mass

See Presentation for more detail. See also 10 Patients with Neck Masses: Identifying Malignant versus Benign, a Critical Images slideshow, to help identify several types of masses.

Diagnosis

The following laboratory studies may be warranted:

  • Complete blood count
  • Serum chemistries (including calcium, phosphate, and uric acid)
  • Liver function tests (including lactate dehydrogenase)
  • Erythrocyte sedimentation rate (in HL)
  • HIV and hepatitis B and C viruses (as clinically indicated)

The following imaging studies may be warranted:

  • Chest radiography (essential)
  • Computed tomography (CT) of the chest, abdomen, or pelvis (necessary for mediastinal, retroperitoneal, and mesenteric adenopathy)
  • CT scanning of the head and neck (mandatory for a head and neck presentation; localized disease; or cranial neuropathies, hearing loss, vertigo, or visual changes)
  • Magnetic resonance imaging (MRI; indicated for evaluating the brain or spinal cord)
  • Positron emission tomography (PET; as indicated)

Other tests to be considered include the following:

  • Immunohistochemical analysis of the tumor (essential)
  • Cytogenetic analysis (useful in select cases)
  • Polymerase chain reaction analysis
  • Fluorescent in-situ hybridization

The following procedures may be helpful:

  • Nasopharyngeal laryngoscopy (essential)
  • Fine-needle aspiration cytology (essential)
  • Excisional lymph-node biopsy (essential in HL and NHL)
  • Bone marrow aspiration and biopsy (essential).
  • Lumbar puncture and cerebrospinal fluid (CSF) analysis
  • Staging laparotomy or laparoscopy for HL
  • Diagnostic tonsillectomy (if lymphoma of the tonsils is suspected)

A lymphoma specialist should perform staging and treatment. The Ann Arbor staging system is used to stage lymphomas.

See Workup for more detail.

Management

Initial therapy for HL typically includes the following:

  • Stage I or II favorable disease – Combined chemotherapy and radiation or combined chemotherapy alone
  • Stage I or II unfavorable disease – Chemotherapy with or without radiation
  • Stage III or IV disease – Combination chemotherapy (eg, ABVD); more intensive regimens (eg, Stanford V and BEACOPP) are being investigated
  • Nodular lymphocyte predominant HL – Radiation or rituximab alone is often used; advanced-stage disease is usually treated like HL in patients with an unfavorable prognosis

Therapy for relapsing or refractory HL typically involves the following:

  • Early-stage disease and relapse after radiation therapy alone – ABVD
  • Relapse after combined-modality therapy or chemotherapy alone – The same or other combination chemotherapy (if remission duration > 12 months)
  • Salvage therapy – ABVD, ESHP, ICE, or DA-EPOCH
  • Failed induction or relapse within a year of initial chemotherapy – High-dose chemotherapy (with or without radiotherapy) followed by autologous hematopoietic stem-cell transplantation

Therapy for NHL may include the following:

  • Indolent B-cell lymphoma (eg, follicular and small lymphocytic lymphoma) – Watch-and-wait strategy initially; fludarabine, anti-CD20, CHOP, rituximab, or rituximab plus CHOP (R-CHOP); on an investigational basis, radioimmunotherapy or stem-cell transplantation
  • Stage I or II DLCBL – Combined modalities; use of rituximab, DA-EPOCH, or both may eliminate the need for irradiation
  • Stage III or IV DLBCL – Combination chemotherapy (eg, CHOP and, subsequently, R-CHOP)
  • Relapsing DLBCL – Salvage chemotherapy (eg, rituximab and ICE [R-ICE], ESHAP, or rituximab and DA-EPOCH [DA-EPOCH-R}; responsive disease is often treated with autologous stem-cell transplantation
  • Primary central nervous system (CNS) lymphoma – Methotrexate, rituximab, irradiation
  • Other aggressive B-cell lymphomas – Burkitt lymphoma is treated with intensive systemic chemotherapy; mantle-cell lymphoma is treated with measures ranging from aggressive combination chemotherapy to allogeneic transplantation; bortezomib may prove effective

Therapy for T-cell lymphomas may include the following:

  • Extranodal NK/T-cell lymphoma, nasal type – Irradiation (for localized disease)
  • Anaplastic large-cell lymphoma – Systemic chemotherapy
  • Angioimmunoblastic T-cell lymphoma – Poor results with standard therapy
  • T-cell lymphoblastic lymphoma – Intrathecal chemotherapy

Surgery for treatment of lymphomas of the head and neck is only performed in select cases.

See Treatment and Medication for more detail.

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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.

The image below depicts a lymphoma of the head and neck.

CT scan of a patient with a natural killer (NK)/T- CT scan of a patient with a natural killer (NK)/T-cell lymphoma of the right nasal cavity and maxillary sinus.
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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 classical
    • Mixed cellularity classical
    • Lymphocyte-rich classical
    • Lymphocyte-depleted classical
  • 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
      • Primary cutaneous follicle center lymphoma
      • Mantle-cell lymphoma
      • Diffuse large B-cell lymphoma (DLBCL)
      • Primary mediastinal (thymic) large B-cell lymphoma
      • Intravascular large B-cell lymphoma
      • ALK positive large B-cell lymphoma
      • Plasmablastic lymphoma
      • Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease
      • Primary effusion lymphoma
      • Burkitt lymphoma
      • Lymphomatoid granulomatosis
  • 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-associated T cell lymphoma
      • Hepatosplenic T-cell lymphoma
      • Subcutaneous panniculitis-like T cell lymphoma
      • Mycosis fungoides
      • Sezary syndrome
      • Primary cutaneous CD30 positive T-cell lymphoproliferative disorders
      • Primary cutaneous peripheral T-cell lymphomas, rare subtypes
      • Peripheral T cell lymphoma, not otherwise specified (NOS)
      • Angioimmunoblastic T cell lymphoma
      • Anaplastic large cell lymphoma
  • Immunodeficiency-associated lymphoproliferative disorders
    • Lymphomas associated with HIV infection
    • Post-transplant lymphoproliferative disorders (PTLD)
    • Lymphoproliferative diseases associated with primary immune disorders
    • Other iatrogenic immunodeficiency-associated lymphoproliferative disorders

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.

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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.

A study by Han et al using the Surveillance, Epidemiology, and End Results (SEER) database found overall survival rates in the United States for nasopharyngeal lymphoma to be 70%, 57%, and 45% at 2, 5, and 10 years, respectively, and determined median overall survival to be 8.2 years. Multivariate analysis indicated that overall and disease-specific survival rates are worse in patients with advanced age or NK/T-cell NHL and are improved in association with radiation therapy. [1]

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Epidemiology

Frequency

United States

Lymphoma is the fifth most common cancer in the United States, with an annual incidence of 74,490 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) [2] ; an increase in the detection of lymphoma; an increase in the elderly population; 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.

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 is 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.

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