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.
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A nodal presentation of HL typically includes one 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 exists that is larger than 1 cm and 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.
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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. A retrospective study that included 740 patients (170 adults and 570 children) undergoing tonsillectomy with pathologic evaluation found an incidence of 0.67% (1.2% adult) for occult malignancy. The investigators described one case of Burkitt lymphoma, one of follicular lymphoma, one of DLBCL, and two of Mantle cell lymphoma. [8]
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.
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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 EBV 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 the video below of a fiberoptic examination of an NK/T-cell lymphoma in the right nasal cavity and maxillary sinus.)
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Fiberoptic nasal examination of a patient with natural killer (NK)/T-cell lymphoma of the right nasal cavity and maxillary sinus.
- A form of subcutaneous T-cell lymphoma resembling a panniculitis has been described (subcutaneous panniculitis-like T-cell lymphoma) in a young man with unilateral cheek swelling, a presentation that could easily be confused with an infectious etiology. [9]
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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 and often arises in the setting of autoimmune thyroiditis.
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Advanced disease can cause facial edema and Horner syndrome.
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Extranodal marginal-zone B-cell lymphoma of MALT lymphoma occurs in the head and neck, in the ocular adnexa, and in thyroid areas. MALT lymphomas in the ocular adnexa can be associated with chlamydial infections and require polymerase chain reaction (PCR) assay analysis. H pylori infections can also be associated with MALT lymphomas.
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Patients with Sjögren syndrome are at increased risk for MALT lymphomas in the oral mucosa.
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Lymphoma involving the base of the skull or CNS can cause cranial nerve palsies, facial pain, hearing loss, vertigo, proptosis, or visual symptoms.
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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.
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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.
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Superior vena cava (SVC) syndrome and pleural effusions may be due to a mediastinal mass.
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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.
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Chromosomal abnormalities are common in lymphomas.
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Aneuploidy occurs in HL, and translocations and deletions mark NHL, such as the C-MYC translocation of Burkitt lymphoma and the BCL2 translocation found in most follicular lymphomas.
Infectious agents implicated in the pathogenesis of some lymphomas include EBV, HIV-1 (aggressive NHL occurs in 10-30% of patients with AIDS), H 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.
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Hashimoto disease increases a patient's risk for thyroid lymphoma, usually aggressive NHL, about 70-fold.
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In general, patients with autoimmune diseases, such as rheumatoid arthritis, have an increased risk for lymphoma.
Immunosuppressive medications, such as those used following organ allotransplantation, increase the risk of EBV-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.
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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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CT scan 6 months after treatment with 4 cycles of DA-EPOCH (ie, infused etoposide, doxorubicin, and vincristine with bolus cyclophosphamide and prednisone).
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CT scan of a patient with a recurrence of stage I-AE angiocentric lymphoma of the left maxillary sinus, treated 7 years earlier with 4 cycles of ProMACE-MOPP (ie, prednisone, methotrexate, Adriamycin, cyclophosphamide, etoposide–mechlorethamine [nitrogen mustard], vincristine, procarbazine, and prednisone) and 3960 cGy of radiation.
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CT scan 2 years after salvage therapy.
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Fiberoptic nasal examination of a patient with natural killer (NK)/T-cell lymphoma of the right nasal cavity and maxillary sinus.
