Differential Diagnosis

The patient presents with a complex set of symptoms including swollen lymph nodes, fatigue, appetite loss, nausea, lightheadedness, and fever. Given the duration and progression of symptoms, along with the laboratory and imaging findings, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis
  • Chronic Lymphocytic Leukemia (CLL) or Non-Hodgkin Lymphoma (NHL) (40%): The gradual onset and progression of symptoms, particularly the slow growth of lymph nodes over three years, along with systemic symptoms like fatigue and recent appetite loss, are concerning for a lymphoproliferative disorder. The appearance of new lymph nodes, including a left supraclavicular node, is especially worrisome for lymphoma. Although the mono titer test was borderline positive and could suggest infectious mononucleosis, the chronic nature of symptoms and the lack of improvement with antibiotics make CLL or NHL more likely. The negative EBV antibody test from a couple of months ago reduces the likelihood of a current EBV infection causing these symptoms, but past infection could still be relevant.
• Other Likely Diagnoses
  • Tuberculosis (TB) (20%): Despite the normal CRP, ESR, and LDH, TB can present with a wide range of systemic symptoms including fever, fatigue, appetite loss, and lymphadenopathy. The lack of response to antibiotics and the presence of systemic symptoms keep TB in consideration, especially if the patient has been exposed or is from an endemic area.
  • Hodgkin Lymphoma (15%): This diagnosis is considered due to the lymphadenopathy, particularly the supraclavicular node, and systemic symptoms like fever and night sweats (though not explicitly mentioned, the fever could be a substitute indicator). Hodgkin lymphoma can have a more gradual onset than other lymphomas and often presents with lymphadenopathy.
  • Autoimmune Disorders (e.g., Rheumatoid Arthritis, Lupus) (10%): Although the inflammatory markers (CRP, ESR) are normal, some autoimmune diseases can present with lymphadenopathy, fatigue, and systemic symptoms. The absence of specific autoantibodies or more characteristic symptoms (e.g., joint pain, skin rashes) makes this less likely but still worth considering.
• Do Not Miss Diagnoses
  • HIV Infection (5%): Given the prolonged period of systemic symptoms and lymphadenopathy, HIV should be considered, especially if there are risk factors for HIV exposure. The borderline positive mono test could also be seen in the context of HIV infection, where EBV reactivation can occur.
  • Sarcoidosis (5%): This condition can cause lymphadenopathy, fatigue, and systemic symptoms. Although less common, it's a diagnosis that should not be missed due to its potential for significant morbidity if left untreated.
• Rare Diagnoses
  • Castleman Disease (2%): A rare disorder that can present with lymphadenopathy, systemic symptoms, and can be associated with HIV or HHV-8 infection. It's less likely but should be considered in the differential due to its potential severity.
  • Lymphoma associated with other conditions (e.g., Sjögren's syndrome, Hashimoto thyroiditis) (3%): Certain autoimmune conditions increase the risk of developing lymphoma. While the primary symptoms do not strongly suggest these conditions, they are part of a broad differential for lymphadenopathy and systemic symptoms.

Justification

The percentages assigned to each category are approximate and based on the clinical presentation, the chronic nature of symptoms, and the results of initial investigations. The single most likely diagnosis and other likely diagnoses are prioritized based on the combination of lymphadenopathy, systemic symptoms, and the lack of response to initial antibiotic treatment. The "Do Not Miss" category includes diagnoses that are potentially life-threatening or significantly impactful if not identified and treated promptly. Rare diagnoses, while less likely, are included to ensure a comprehensive approach to the differential diagnosis.