What is the most likely diagnosis for an HIV (Human Immunodeficiency Virus) positive patient with a rapidly enlarging neck mass?

Most Likely Diagnosis: HIV-Associated Lymphoma

In an HIV-positive patient presenting with a rapidly enlarging neck mass, lymphoma is the most likely diagnosis, specifically diffuse large B-cell lymphoma (DLBCL) or Burkitt lymphoma, which are the most common HIV-associated lymphomas affecting the head and neck region. 1, 2, 3

Why Lymphoma is the Primary Concern

Epidemiologic Evidence

• Non-Hodgkin lymphoma (NHL) is the second most common malignancy in HIV patients after Kaposi's sarcoma, with incidence rates vastly exceeding the general population 1, 2
• The risk for lymphoma in HIV-infected patients is directly related to immunosuppression, cytokine dysregulation, and co-infection with lymphotrophic viruses, particularly Epstein-Barr virus (EBV) 2, 3
• Even with highly active antiretroviral therapy (HAART), the incidence of DLBCL remains significantly elevated in HIV patients compared to the general population 4

Clinical Presentation Characteristics

• HIV-associated lymphomas characteristically present with rapid progression, frequent extranodal involvement, and aggressive behavior 1, 2
• These lymphomas typically present with advanced stage disease, bulky masses with high tumor burden, and commonly involve extranodal sites including the head and neck region 2, 3
• The "rapidly enlarging" nature described in this case is pathognomonic for aggressive lymphoma behavior in the HIV population 1, 4

Specific Lymphoma Subtypes to Consider

Most Common Types

• Diffuse large B-cell lymphoma (DLBCL) with immunoblastic-plasmacytoid differentiation is among the most frequent HIV-associated lymphomas 3
• Burkitt lymphoma (BL) is also highly prevalent in HIV patients and presents with rapid growth 3
• Both frequently carry EBV infection and display plasma cell-related phenotypes 3

HIV-Specific Lymphomas

• Plasmablastic lymphoma of the oral cavity type occurs specifically in HIV-positive patients and can present as neck masses 3, 5
• Primary effusion lymphoma (PEL) and its solid variants are KSHV-associated and occur with profound immunosuppression 3

Differential Diagnosis Considerations

Why Not Head and Neck Squamous Cell Carcinoma (HNSCC)?

While HNSCC must be considered in any adult neck mass, several factors make lymphoma more likely in this HIV-positive patient:

• The "rapidly enlarging" descriptor strongly favors lymphoma over HNSCC, which typically has a more indolent growth pattern 6, 1
• HNSCC risk factors (age >40, tobacco/alcohol use) are not mentioned in this case 6
• HIV status itself dramatically increases lymphoma risk more than HNSCC risk 2

Infectious Etiologies

• While HIV patients are susceptible to opportunistic infections causing lymphadenopathy, the "rapidly enlarging" nature makes malignancy more concerning 6
• Any neck mass in an HIV patient should NOT be empirically treated with multiple courses of antibiotics without tissue diagnosis, as this delays cancer diagnosis and worsens outcomes 6, 7

Diagnostic Workup Algorithm

Immediate Steps Required

1. Perform excisional biopsy (preferred) or fine-needle aspiration (FNA) to establish tissue diagnosis 6

   • Excisional biopsy evaluated by an expert hematopathologist using immunohistochemistry and molecular techniques is the gold standard 6
   • FNA should be performed instead of open biopsy initially if the diagnosis remains uncertain 6

2. Obtain contrast-enhanced CT or FDG-PET/CT for staging 6

   • FDG-PET/CT provides higher sensitivity, especially for extranodal disease 6
   • Caution: FDG-PET/CT may have higher false-positive rates in HIV patients due to immune deficiency-related lymphoid hyperplasia and suppressed infections 6

3. Complete blood count with differential to assess for lymphoma or immunosuppression 6

4. EBV antibody titers given the strong association between EBV and HIV-associated lymphomas 6, 3

Additional Evaluation

• Bone marrow biopsy for complete staging 6
• Assessment of HIV viral load and CD4 count to evaluate degree of immunosuppression 6
• If CNS symptoms present, MRI brain to exclude CNS involvement 6

Critical Pitfalls to Avoid

Most Dangerous Error

The most catastrophic mistake is assuming this mass is infectious and prescribing antibiotics without definitive diagnosis, which delays lymphoma diagnosis and significantly worsens prognosis 6, 7

Diagnostic Challenges Specific to HIV Patients

• Early diagnosis is challenging due to atypical presentation and coexisting opportunistic infections 4
• Imaging findings may be atypical, and lymphoma diagnosis is often unexpected as clinicians initially investigate for presumed infection 4
• Do not assume cystic neck masses are benign—continue evaluation until diagnosis is obtained, as HIV-associated lymphomas can present with cystic features 6

Treatment Considerations

• Treatment approaches are complicated by comorbid opportunistic infections and patient performance status 4
• Treatment failure and early relapse are common in AIDS-related lymphoma 4
• Prognosis is generally worse than similar aggressive lymphomas in immunocompetent patients, though HAART has improved outcomes 2