AIDS-Related Lymphomas Workup

Updated: Dec 01, 2015
  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
  • Print

Laboratory Studies

The following laboratory investigations are required to diagnose the AIDS-related lymphoma (ARL):

  • Histopathology of the biopsied lymph node or other biopsied specimen – Fine-needle aspiration (FNA) is not advisable for diagnostic purposes. [65]
  • Immunophenotyping and flow cytometry for cell surface markers (see the image below) [66]
    2-Dimensional (2-D) flow cytometry. These images d 2-Dimensional (2-D) flow cytometry. These images demonstrate the highlighted cells to be CD5 negative, CD23 negative, as well as lambda negative. The cells are typically CD19+, CD20+, CD22+, and CD10+.

The following investigations help in the management of the patient with AIDS-related lymphoma (ARL):

  • Complete blood cell (CBC) count, differential, platelets – The results may show varying degrees of anemia that may be secondary to marrow infiltration or anemia of chronic disease. The platelet count may be low because of marrow infiltration or splenomegaly. Leukopenia may be present, especially in advanced stages.
  • Comprehensive metabolic panel – Abnormal liver-related test results may occur because of hepatic involvement. This panel also provides an impression about baseline renal function.
  • Uric Acid – Uric acid levels increase in tumor lysis syndrome. By Cairo-Bishop criteria, the measurements may increase by 25% or >8 mg/dL.
  • Lactase dehydrogenase (LDH) and beta-2 microglobulin – LDH levels correlate with tumor burden and are an important prognostic marker in lymphoma patients. [67] LDH levels increase in cell breakdown, and lymphoma cells have a high rate of turnover, hence, they have elevated LDH activity. Beta-2 microglobulin is another important marker for prognostic reasons and also correlates with tumor burden. [67]
  • Hepatitis B – Hepatitis B testing is important, considering the risk of reactivation upon the institution of chemotherapy and immunotherapy. If the screening indicates the presence of infection, patients need hepatitis B virus (HBV) viral load and gastroenterology input. [68]  Hepatitis B serology is standard of care if anti-CD20 therapy such as Rituximab is to be used to treat lymphoma due to risk of reactivation of Hepatitis B [95] .
  • Hepatitis C -- Serology and if positive, viral load/genotype should be established in all patients at diagnosis this is now highly curable and has implications for toxicity and chemotherapy [94] .

Imaging Studies

Lung involvement

Chest x-rays have a limited role in ruling out or establishing baseline and  (CT) scans of the chest in these patients should be done to improve diagnostic yield. [69]

Commonly noted abnormalities on the chest x-ray and CT include the following:

  • Hilar and/or mediastinal lymphadenopathy
  • Pleural effusions
  • Mass lesion
  • Lobar consolidation
  • Pleural thickening

Gastrointestinal tract

CT scanning is the imaging modality of choice for the detection of intra-abdominal lymphomas. CT scan findings of lymphomas of the gastrointestinal wall may show solitary masses, bowel wall thickening, and cavitary lesions. These findings may be found in up to 80% of lymphomas of the small intestine. [70] Endoscopic ultrasonography may be used in cases of gastric lymphomas.

Primary CNS lymphoma (PCNSL)

A PCNSL is typically a well-defined focal lesion on a head CT scan. AIDS-related PCNSLs show a high degree of enhancement on CT scans following intravenous contrast injection. The enhancement is typically irregular, unlike that in seronegative patients with the same neoplasm. The difference might be attributable to central necrosis of the tumor in AIDS patients because of rapid growth when compared with non-HIV positive patients. Magnetic resonance (MRI) scanning improves the diagnostic yield, especially when done with intravenous contrast. [71]

Testicular involvement

Ultrasonography can detect mass lesions in the scrotum. It is important to note that ultrasonography of the opposite testis should also be done in patients with testicular tumors. [72]

Bone involvement

Bone scanning may be done in patients with a history that is suggestive of skeletal involvement and in the presence of high alkaline phosphatase (ALP) levels. MRI may also be used to evaluate vertebral involvement by the lymphoma (see the image below). It is important to know that involvement of the marrow itself by the tumor may be patchy and thus missed in the biopsy. In such patients, MRI may reveal the bone marrow lesions. [73]

Gallium scans of a patient diagnosed with small, n Gallium scans of a patient diagnosed with small, noncleaved cell lymphoma (SNCCL). These scans show a prominent area of increased uptake in the right cervical region that is suggestive of a gallium-avid tumor.

Other Tests

Positron emission tomography (PET) scanning

PET scans have been shown to be very sensitive and specific for the staging of patients with ARLs and also for following such patients for a response to therapy. However, PET scans can be falsely positive, as other organs in addition to tumors can also pick up radioactive fluorodeoxyglucose (FDG). Also, the yield is lower for lesions that are smaller than 1 cm. PET scanning is done in conjunction with CT scanning. [74]

Multiple uptake gated acquisition (MUGA) scanning / Echocardiography

These studies are indicated when the treatment plan includes cardiotoxic chemotherapeutic agents, like anthracyclines. [75]

Immunohistochemical analysis can establish the lymphoma subtype and molecular genetic analysis or fluorescent in situ hybridization (FISH) can be used to detect gene rearrangements. [76]



See the list below:

  • Diagnostic biopsy – Biopsy and subsequent evaluation of the specimen by a pathologist is the gold standard of diagnosis for AIDS-related lymphomas (ARLs). FNA is not sufficient for this purpose in the case of lymphomas. [65]
  • Bone marrow aspirate and biopsy – Bone marrow examination is not aimed at diagnosis; rather, more often it is done to evaluate involvement of the marrow. [77]
  • Lumbar puncture – All patients with HIV and a lymphoma should have a lumbar puncture with microscopy and flow-cytometry performed to rule out CNS involvement.

Histologic Findings

Pathologically, AIDS-related lymphomas (ARLs) are composed almost exclusively of B-cell tumors of the aggressive type, including diffuse, large B-cell lymphoma; immunoblastic lymphoma; and small, noncleaved lymphoma, either Burkitt or Burkitt-like.

The common morphologic features of diffuse, large B-cell lymphoma are a relatively large cell size and a diffuse pattern of growth. The cells are about 4 to 5 times larger than a small lymphocyte and usually have a round, vesicular nucleus. The nucleoli are variable in number and position (ie, they may be single and central or peripheral and multiple). The cytoplasm is pale or basophilic. (See the images below.)

Diffuse large B cell lymphoma under low magnificat Diffuse large B cell lymphoma under low magnification showing diffuse proliferation of large atypical lymphoid cells in this lymph node specimen.
Diffuse large B cell lymphoma under high power sho Diffuse large B cell lymphoma under high power showing cells that have moderate to abundant cytoplasm, round to irregular nuclear contour, vesicular nuclear chromatin and one to multiple nucleoli. Scattered small mature lymphocytes are seen. Green arrows = atypical lymphocytes; yellow arrows = small lymphocytes.

Immunoblastic lymphoma has malignant lymphoma cells with plasmacytic features. The cells have large, solitary nucleoli and abundant cytoplasm. The tumor cells usually show strong cytoplasmic immunoreactivity with monoclonal antibody against syn-1.

Plasmablastic lymphoma forms cohesive masses and has large neoplastic cells. The malignant cells have a "squared off" appearance. The nucleus may be centrally or eccentrically placed.

Burkitt lymphoma or small, noncleaved cell lymphoma has medium-sized tumor cells with a monotonous appearance. The nuclei are round and contain multiple, centrally located nucleoli. The cytoplasm is usually mildly basophilic. The tumor has a high cell turnover, with a large number of mitotic figures and dead cells. Benign macrophages with debris ingested from dead cells may be found within the microscopic field, giving rise to a "starry sky" pattern. (See the images below.)

Burkitt lymphoma under low magnification showing s Burkitt lymphoma under low magnification showing sheets of atypical mononuclear cells. Scattered macrophages can be seen (as demonstrated by the green arrows) giving rise to classical "starry-sky" pattern.
Burkitt lymphoma under high magnification showing Burkitt lymphoma under high magnification showing sheets of atypical mononuclear cells. The cells are intermediate to large in size with scant cytoplasm, round to irregular nuclear contour, smudged chromatin and some with nucleoli. Mitosis and apoptosis are frequent with scattered macrophages giving focal "starry-sky" pattern. Green arrows = macrophages; yellow arrows = mitosis.

Primary effusion lymphoma cells have irregularly shaped nuclei and multiple nucleoli. The cells are variably chromatic.



Table. Lymphomas are staged according to the Ann Arbor Staging System, as follows (Open Table in a new window)

Stage Definition
I Only a single lymph node region is involved.
IE A single extralymphatic site or organ is involved.
II Two or more lymph node regions are involved on the same side of the diaphragm.
IIE A single extranodal site and adjacent nodes are involved.
III Nodal regions on both sides of the diaphragm are involved.
IIIE Stage III, plus a single extranodal site is involved.
IIIS Stage III, plus spleen involvement
IIISE Stage III, plus a single extranodal site and spleen are involved.
IV Liver, brain, or bone marrow involvement

Diffuse or disseminated involvement of one or more extralymphatic organs


A or B classification


The disease is classified as "B," if B symptoms (eg, fevers, night sweats, or unexplained weight loss >10%) is present. If none of these symptoms are present, the disease is classified as "A."


Staging is not usually valuable for PCNSLs and primary effusion lymphomas and thus is not indicated. The malignancy generally remains confined within the originating body cavity in the PCNSLs and in the CNS in primary effusion lymphomas. [78]