What is the best initial diagnostic test for a new left inguinal mass in a patient with HIV (Human Immunodeficiency Virus) infection and a history of highly active antiretroviral therapy (HAART)?

Excisional Biopsy is the Recommended Diagnostic Test

For a new inguinal mass in an HIV-infected patient with well-controlled disease on HAART, excisional biopsy should be performed to establish a definitive tissue diagnosis. 1

Rationale for Excisional Biopsy

The most recent and highest-quality guideline from the European Hematology Association and European Society for Medical Oncology (2024) explicitly states that lymphoma should be diagnosed via tumor biopsy, preferably excisional, that is evaluated by an expert haematopathologist using immunohistochemistry and molecular techniques. 1 This recommendation prioritizes morbidity and mortality outcomes by ensuring accurate diagnosis of potentially life-threatening malignancies.

Why This Patient Requires Tissue Diagnosis

• This patient presents with a new, discrete 4 cm left inguinal mass that differs from his chronic diffuse lymphadenopathy, raising concern for lymphoma or other malignancy 1
• Despite well-controlled HIV (undetectable viral load, CD4 >200 cells/μL), HIV-infected patients remain at substantially elevated risk for lymphomas, even on effective HAART 1
• The distinction between benign lymphoid hyperplasia and malignancy cannot be reliably made without histopathologic examination 1

Why Other Options Are Inadequate

FDG-PET Scan (Option A)

• While FDG-PET/CT provides higher sensitivity for staging lymphoma, it has a higher false-positive rate in HIV patients due to immune deficiency-related lymphoid hyperplasia and suppressed HIV infection 1, 2
• PET scanning is appropriate for staging after tissue diagnosis is established, not as the initial diagnostic test 1
• FDG-avid lesions in HIV patients should be re-biopsied if there is doubt about their significance 1

Core Biopsy (Option B)

• While core biopsy can provide tissue, excisional biopsy is preferred because it provides more tissue for comprehensive immunohistochemistry and molecular analysis required for lymphoma classification 1
• The 2024 EHA-ESMO guidelines specifically recommend excisional biopsy as the preferred approach 1

Fine Needle Aspiration (Option C)

• FNA with cytology alone is insufficient for lymphoma diagnosis 1
• The guidelines state that diagnosis by cytology and flow cytometry should only be used "in exceptional cases when no tumour mass can be biopsied" 1
• A 4 cm accessible inguinal mass is clearly amenable to excisional biopsy, making FNA inappropriate 1

Clinical Algorithm for New Masses in HIV Patients

1. Recognize the clinical scenario: New discrete mass distinct from chronic lymphadenopathy in HIV patient 1
2. Perform excisional biopsy of the accessible mass for definitive diagnosis 1
3. Ensure expert haematopathology review with immunohistochemistry and molecular techniques 1
4. If lymphoma is diagnosed, proceed with staging FDG-PET/CT, bone marrow biopsy, and CNS evaluation as indicated 1
5. Continue HAART throughout the diagnostic and treatment process to maintain viral suppression 1

Important Pitfalls to Avoid

• Do not rely on imaging alone for diagnosis in HIV patients, as false-positive results from reactive lymphoid hyperplasia are common 1, 2
• Do not assume chronic lymphadenopathy explains a new, enlarging mass—this requires tissue diagnosis to exclude malignancy 1
• Do not use FNA as the primary diagnostic approach when excisional biopsy is feasible, as it provides insufficient tissue for comprehensive lymphoma classification 1
• Do not delay biopsy to perform staging studies first—tissue diagnosis must come before staging 1