Differentials
Hodgkin's lymphoma
SIGNS / SYMPTOMS
Peak incidence 20-34 years.
Hodgkin's lymphoma may present with generalised pruritus or alcohol-induced pain at the site of a tumour mass.
Hodgkin's lymphoma tends to spread from one lymph node chain to another in contiguous fashion. Involvement of Waldeyer ring and extranodal sites is less common in Hodgkin's lymphoma.
Very difficult to differentiate clinically.
INVESTIGATIONS
Lymph node biopsy (positive for Reed-Sternberg cells).[114]
Acute lymphoblastic leukaemia (ALL)
SIGNS / SYMPTOMS
Acute onset, ecchymoses, petechiae, easy bruising, bleeding, and infection are key presenting symptoms.
INVESTIGATIONS
Peripheral blood smear (positive for leukaemic lymphoblasts), bone marrow biopsy (positive for leukaemic lymphoblasts), flow cytometry/immunohistochemistry (positive for tumour cell markers for ALL), cytogenetics (positive for Philadelphia chromosome), polymerase chain reaction (positive for BCR::ABL1 fusion gene).
Infectious mononucleosis
SIGNS / SYMPTOMS
A self-limiting condition that tends to present in young adults (high school and university students). There is generally abrupt onset of symptoms including fever, pharyngitis, rash, and myalgias.
Lymphadenopathy/splenomegaly is acute and reactive, and tender (in contrast to non-tender nature of lymphadenopathy and splenomegaly in lymphoma).
INVESTIGATIONS
Epstein-Barr virus serological test (positive), heterophile antibody test (monospot test, positive), polymerase chain reaction for EBV DNA (positive).
Hepatitis C (HCV)
SIGNS / SYMPTOMS
History of intravenous drug use, HIV, multiple transfusions.
Abdominal pain, nausea, symptoms of liver disease, and malaise are common presenting features. Can be asymptomatic.
INVESTIGATIONS
HCV-antibody enzyme immunoassay test (positive).
Polymerase chain reaction for HCV RNA (positive).
Cytomegalovirus infection (CMV)
SIGNS / SYMPTOMS
Immunocompromised hosts (e.g., post-transplant) are usually symptomatic.
Visual symptoms, fever, nausea and vomiting, and diarrhoea are common presenting features.
Immunocompetent individuals with CMV are usually asymptomatic.
INVESTIGATIONS
CMV serology (positive), polymerase chain reaction/quantitative nucleic acid testing (positive for CMV), biopsy (positive for CMV).
Tuberculosis
SIGNS / SYMPTOMS
May be difficult to differentiate clinically.
Patients may have risk factors for tuberculosis (e.g., HIV positive; history of drug use; malnutrition; residence in high-risk congregate setting [e.g., homeless shelter]; low socio-economic status; residence in a tuberculosis-endemic country).
Cough, fever, malaise, anorexia, and weight loss are common presenting features.
INVESTIGATIONS
Chest x-ray, CT chest, tuberculin skin test (positive), interferon gamma release assay (positive), acid-fast bacilli smear (positive), tuberculosis culture (positive), pleural/peritoneal fluid analysis (in some cases), pleural biopsy (in some cases), tissue biopsy (in some cases).
HIV infection
SIGNS / SYMPTOMS
Risk factors for sexually transmitted disease (e.g., unprotected sexual intercourse); history of HIV-infected blood transfusion, intravenous drug use, or percutaneous needle stick injury; prior flu-like illness and rash.
INVESTIGATIONS
Enzyme-linked immunosorbent assay (positive HIV screen), HIV antibody differentiation immunoassay (positive for HIV-1 or HIV-2 antibodies; positive for HIV antibodies [undifferentiated]), reverse transcription polymerase chain reaction (positive for HIV RNA).
Syphilis infection
SIGNS / SYMPTOMS
Risk factors for sexually transmitted disease (e.g., sexual contact with an infected person); history of illicit drug use; prior genital chancre and rash.
INVESTIGATIONS
Treponema-specific test (e.g., positive treponemal enzyme immunoassay [EIA]); Treponema-non-specific test (e.g., positive rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]).
Sarcoidosis
SIGNS / SYMPTOMS
Young or middle-aged.
Cough, dyspnoea, skin lesions, ocular symptoms (e.g., photophobia), and fatigue/malaise are common. Facial palsy may be present. May be asymptomatic
INVESTIGATIONS
Chest x-ray, CT chest (hilar adenopathy), endobronchial ultrasound-guided transbronchial needle aspiration or skin biopsy (non-caseating granulomas).
Rheumatoid arthritis
SIGNS / SYMPTOMS
More common in females.
Joint symptoms (pain, swelling, heat, stiffness) are characteristic features.
INVESTIGATIONS
Rheumatoid factor (positive), anti-cyclic citrullinated peptide antibody test (positive), erythrocyte sedimentation rate (elevated), C-reactive protein level (elevated) imaging (synovitis).
Systemic lupus erythematosus
SIGNS / SYMPTOMS
Much more common in females.
Characteristic features include malar (butterfly) rash, photosensitivity, skin lesions, oral ulcers, myalgia, arthritis, and neurological symptoms.
INVESTIGATIONS
Antinuclear antibody (positive), anti-double-strand DNA antibodies (positive), anti-Smith antibodies (positive), urinalysis (haematuria, proteinuria).
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