Lymphomas of the Head and Neck Workup

Updated: Mar 03, 2022
  • Author: Jordan W Rawl, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Laboratory Studies

The following laboratory studies are indicated:

  • Complete blood cell count

  • Serum chemistries, including calcium, phosphate, and uric acid levels

  • Liver function, including lactate dehydrogenase values (an elevated level of lactate dehydrogenase is a biomarker of adverse prognosis)

  • Erythrocyte sedimentation rate (ESR) in HL

  • HIV and hepatitis B and C viral panels, as clinically indicated


Imaging Studies

Chest radiography is essential.

CT scanning of the chest, abdomen, and/or pelvis is necessary for the evaluation of mediastinal, retroperitoneal, and mesenteric adenopathy. CT scans miss splenic involvement in 20-30% of cases of limited stage HL.

CT scanning of the head and/or neck is mandatory for patients with a head and neck presentation; localized disease; or symptoms such as cranial neuropathies, hearing loss, vertigo, or vision changes. The images below depict CT scan changes.

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.
CT scan 6 months after treatment with 4 cycles of CT scan 6 months after treatment with 4 cycles of DA-EPOCH (ie, infused etoposide, doxorubicin, and vincristine with bolus cyclophosphamide and prednisone).
CT scan of a patient with a recurrence of stage I- 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.
CT scan 2 years after salvage therapy. CT scan 2 years after salvage therapy.

MRI is used as indicated for evaluation of the brain and/or spinal cord. PET scanning should also be ordered as indicated.


Other Tests

Immunohistochemical analysis of the tumor is essential for diagnosis and may aid in identifying monoclonal antibody targets such as CD20 (rituximab), CD52 (alemtuzumab), PD-1 (nivolumab, pembrolizumab), or CD30 (brentuximab). Cytogenetic analysis may be useful in select cases.

PCR assay analysis helps in evaluating for B- or T-cell clonality or for minimal residual disease, such as t(14;18).

In DLBCL, fluorescent in-situ hybridization (FISH) for t(8;14)/MYC translocation should be considered. Up to 10% of DLBCLs have a MYC translocation and a poor outcome with standard therapy. [10]

Triple-hit lymphomas (MYC/BCL2/BCL6 translocations) and double-hit lymphomas (MYC/BCL2 vs MYC/BCL6 translocations) have a worse prognosis, particularly if they overexpress p53. [11]



Nasopharyngeal laryngoscopy

Nasopharyngeal laryngoscopy is essential. Perform this as the initial investigation to evaluate for a neoplasm of the upper aerodigestive tract that is accessible for biopsy.

Fine-needle aspiration cytology

Fine-needle aspiration cytology is also essential. This test is useful for the initial investigation of neck lymphadenopathy for differentiating squamous cell carcinoma from lymphomas, thyroid tumors, and salivary gland tumors.

A study by Crous et al found the combination of fine-needle aspiration cytology and flow cytometry to be effective in diagnosing NHL but less so in detecting HL. According to the investigators, in NHL the combined diagnostic means had a sensitivity of 95.5%, a specificity of 99.9%, a positive predictive value of 99.5%, and a negative predictive value of 99.2%, being 99.3% accurate. However, fine-needle aspiration cytology/flow cytometry missed 6 out of 13 HL cases (46.2%). [12]

Excisional lymph-node biopsy

Excisional lymph-node biopsy is essential in HL and NHL. Needle aspiration and/or biopsy are not adequate for the primary histologic diagnosis because the architectural features of the tissue are important. A biopsy specimen should be obtained from the lump through an incision that can itself be excised and incorporated into a radical neck dissection if the histologic findings indicate squamous cell carcinoma. In most cases, the unfixed node should be sent immediately to the laboratory for analysis.

Bone marrow aspiration and biopsy

Bone marrow aspiration and biopsy are also essential. Results are positive in as many as 70% of patients with indolent NHL. In disseminated disease, malignant cells may be found in the bone marrow, spinal fluid, ascites fluid, or pleural fluid.

Lumbar puncture

Lumbar puncture may be indicated. This should be performed routinely in all patients with HIV infection, as well as in patients with specific histologic subtypes such as Burkitt lymphoma and lymphoblastic lymphoma. Lumbar puncture is also used when possible symptoms of CNS disease are present after head CT or MRI shows no evidence of mass effect. In addition to cytology, the cerebrospinal fluid (CSF) should be evaluated with flow cytometry, as evidence has indicated that cytology may not help in detecting some cases with positive results on flow cytometry.

Staging laparotomy or laparoscopy

Historically, staging laparotomy was often included in the initial evaluation of patients with HL, as this was the only way to detect occult splenic disease. This is now being replaced by PET/CT scanning. 

Diagnostic tonsillectomy

Diagnostic tonsillectomy may be indicated if lymphoma of the tonsils is suspected. Risk factors for malignancy in the tonsils are tonsillar asymmetry, a history of cancer, palpable firmness or a visible lesion of the tonsil, neck mass, unexplained weight loss, and constitutional symptoms.

In a study of 476 consecutive adults undergoing tonsillectomy, no patient without at least one of the risk factors listed above had malignancy on pathologic evaluation of the tonsils. However, a retrospective study including 740 patients (170 adults and 570 children) undergoing tonsillectomy with pathologic evaluation had an incidence of 0.67% (1.2% adult) for occult malignancy. One case of Burkitt lymphoma, one case of follicular lymphoma, one case of DLBCL, and two cases of Mantle cell lymphoma were described. Two of the five patients with occult malignancies discovered on routine tonsillectomy did not have any features suggestive of malignancy. [8]


Histologic Findings

Accurate histologic diagnosis is the main guide for the modality of treatment to be used in NHL. A pathologist experienced in lymphoma diagnosis uses immunophenotyping by immunocytochemistry and/or flow cytometry to aid diagnosis. Special stains can be used, such as staining for follicular dendritic cells to highlight residual architecture in differentiating MALT from non-MALT lymphoma. Of interest, 80% of lymph-node infarctions are associated with a final diagnosis of lymphoma.



A lymphoma specialist should perform staging and treatment.

  • The Ann Arbor staging system is used to stage lymphomas. Although it was originally designed for HL and based on the contiguous lymphatic mode of spread of HL, it is used for cases of NHL in which hematogenous dissemination is prevalent. The Ann Arbor staging classification is as follows:

    • Stage I - Involvement of a single lymph node region or lymphoid structure

    • Stage II - Involvement of 2 or more lymph node regions on the same side of the diaphragm or localized contiguous involvement of only 1 extralymphatic site and lymph node region

    • Stage III - Involvement of lymph node regions or lymphoid structures on both sides of the diaphragm and possibly the spleen

    • Stage IV - Disseminated involvement of 1 or more extralymphatic organs with or without lymph node involvement and/or involvement of the bone marrow or liver

  • Other designations are as follows:

    • Letter designations

      • A - Asymptomatic, or B constitutional symptoms: This type is characterized by unexplained, persistent or recurrent fever with temperature higher than 38°C or by recurrent and drenching night sweats within 1 month, or by unexplained loss of more than 10% of the person's body weight within 6 months.

      • E - Extranodal: This form is characterized by limited and direct extension into an extralymphatic organ from an adjacent lymph node.

      • X - Bulky disease: In this form, the width of the mediastinal tumor is greater than one third of the transthoracic diameter at T5/6, or the diameter of the tumor diameter is larger than 10 cm.

    • Stage IV indicates disseminated disease, or multifocal extranodal, bone marrow, or liver involvement. Bone involvement must be separated from bone marrow involvement because the latter is always defined as disseminated disease.

  • The clinical stage is defined by the extent of disease based on physical findings and findings on other noninvasive studies. The pathologic stage is defined by data obtained from invasive tests, including biopsy of specimens obtained from different sites, usually during staging laparotomy.

  • Treatment and prognosis for HL and NHL depend on the disease stage, biomarkers, and tumor biology. In NHL and in some types of HL, the histologic subtype dictates therapy.

  • In the past, early stage HL was usually treated with radiotherapy alone, but now, it is generally treated with a combination of radiotherapy and chemotherapy. Disseminated disease is treated by using chemotherapy with or without radiotherapy.

  • In some patients with indolent NHL who have early stage localized disease, radiotherapy alone may be an option. For aggressive lymphomas, chemotherapy is standard, but may be used in conjunction with radiotherapy. Radiotherapy is the primary treatment modality for early stage NK/T-cell lymphomas.