New Lymphadenopathy in a Woman With a History of Colon Cancer

A 47-year-old woman who recently completed adjuvant chemotherapy for colon cancer has painless cervical lymphadenopathy of 1 to 2 cm. She has no fever, sore throat, cough, or unexplained weight loss, and she denies exposure to ill persons or animals.

HISTORY

Adenocarcinoma of the sigmoid colon was detected during a workup for anemia. A preoperative carcinoembryonic antigen (CEA) level was normal. The patient underwent surgery with curative intent; she received no blood transfusions during the procedure. The operation was followed by 12 weekly treatments with 5-fluorouracil and leucovorin (administered according to the Roswell Park regimen) to reduce her risk of disease recurrence. She has no other significant medical history.

PHYSICAL EXAMINATION

Other than the cervical lymphadenopathy, physical findings are unremarkable. No supraclavicular, axillary, or inguinal lymphadenopathy is detected. There is no hepatosplenomegaly. The patient's surgical wound is completely healed and nontender.

LABORATORY AND IMAGING RESULTS

Her total white blood cell count is 4200/µL, with 51.9% neutrophils and 34.4% lymphocytes. She has mild anemia but without evidence of iron deficiency; no thrombocytopenia is detected. Her CEA level remains normal. Results of a chemistry panel and biochemical profile are also normal.

CT scans, with and without contrast, reveal diffuse adenopathy throughout. No liver or lung lesions are identified. A screening mammogram reveals bilateral axillary lymphadenopathy.

What is the most appropriate next step in the evaluation of this patient?

A. Inform her that metastatic colon cancer has probably developed, and initiate a more aggressive chemotherapy regimen that includes bevacizumab(.
B. Order a biopsy of a cervical lymph node to evaluate the adenopathy.
C. Order a bone marrow biopsy to evaluate her anemia.
D. Order serological tests for inflammatory and infectious conditions such as HIV infection.

Answer on next page

CORRECT ANSWER: D

This patient underwent treatment of her colon cancer with curative intent. Thus, the development of metastatic disease so soon (choice A) is quite unlikely. It is also unlikely that diffuse adenopathy representing either a new or recurrent cancer would appear without other systemic symptoms. In any event, a more definitive diagnosis, based on biopsy results or an elevated CEA level, would be needed before beginning an aggressive chemotherapeutic regimen.

Patients undergoing chemotherapy remain susceptible to other diseases that are prevalent in the population at large. Therefore, alternative causes of this woman's lymphadenopathy were explored. After repeated questioning, she admitted to several sexual encounters with a man who might have been infected with HIV. She was no longer in touch with him.

Symptoms and signs in early HIV infection. Primary HIV infection causes a diverse, nonspecific flu-like syndrome whose symptoms include fever (temperature, 39°C to 40.5°C [102.2°F to 105°F]), sore throat, fatigue, adenopathy, headache, rash, and arthralgia or myalgia. This acute retroviral syndrome is seen in 50% to 90% of patients who undergo HIV seroconversion.^1,2 The time between infection and the onset of the syndrome is usually 2 to 6 weeks. Laboratory abnormalities seen during that time may include transient leucopenia, lymphopenia followed by a CD8⁺ T lymphocytosis, and atypical lymphocytes on a peripheral blood smear. Other nonspecific laboratory abnormalities, such as anemia, thrombocytopenia, and liver enzyme level elevations, may be seen.

Difficulty of diagnosis. Acute retroviral syndrome is frequently confused with mononucleosis or, if a rash is present, with other viral exanthems or secondary syphilis.² The median duration of symptoms is 14 days; only a minority of patients require hospitalization.¹ Unfortunately, because of the nonspecific nature of the symptoms, the diagnosis of primary HIV infection is often missed. This is a serious public health problem.

The difficulty of diagnosis is compounded by the fact that the period immediately following seroconversion is associated with very high levels of circulating HIV but no significant immune response.³ Thus, the results of standard serological testing for HIV antibody, with confirmation by Western blot, may remain indeterminate— or be falsely negative—for 1 to 2 months after infection.^2,3

Effective tests for primary HIV infection. To establish a diagnosis of primary HIV infection in the setting of negative or indeterminate results on antibody tests, laboratory testing for the HIV p24 antigen or quantitative HIV RNA levels must be ordered (choice D). The HIV RNA test is more sensitive than the HIV p24 antigen test, but it is also more expensive.⁴ Although a second antibody test later in the course of the illness is needed to confirm seroconversion, patients with initial negative or indeterminate results on antibody testing but high HIV viral loads can be considered to be infected with HIV.

When is lymph node biopsy warranted? A lymph node biopsy was performed in this patient—probably much too early in the workup. It revealed reactive lymph node, without evidence of tumor or bacterial or mycobacterial infection. Lymph node biopsy of infectious and inflammatory lesions often shows reactive hyperplasia. In some instances, the hyperplasia can be quite striking and can be confused with lymphoma. However, the acute onset and diffuse nature of the adenopathy here suggested a systemic disease; thus, node biopsy (choice B), although not an incorrect maneuver, was not the best next step.

What can a bone marrow biopsy reveal? A bone marrow examination (choice C) would also be a low-yield test in this setting. The patient's anemia might be the result of chemotherapy, HIV infection, or both. Bone marrow is an uncommon metastatic site in colon cancer. Moreover, bone marrow examination is a low-yield test in most infections, even in immunosuppressed patients.⁵

Outcome of this case. The patient underwent appropriate testing. Her viral load was 156,234 copies/mL, and her CD4⁺ cell count was 334/µL; acute HIV infection was diagnosed. Her case serves as a reminder that patients who are being treated for other diseases and those whose older age may not raise suspicion of HIV may yet present with acute HIV infection. A high index of suspicion, regardless of patient age or known or disclosed HIV risk factors, allows for earlier detection.