Differentials
Hodgkin lymphoma
SIGNS / SYMPTOMS
Bimodal age distribution at diagnosis (peak incidence 20-34 years followed by more modest peak among those >55 years), pruritus, and alcohol-induced pain.
Very difficult to differentiate clinically.
INVESTIGATIONS
Lymph node biopsy (positive for Reed-Sternberg cells).[78]
Acute lymphoblastic leukemia (ALL)
SIGNS / SYMPTOMS
Acute onset, ecchymoses, petechiae, easy bruising, bleeding, and infection are key presenting symptoms.
INVESTIGATIONS
Peripheral blood smear (positive for leukemic lymphoblasts), bone marrow biopsy (positive for leukemic lymphoblasts), flow cytometry/immunohistochemistry (positive for tumor cell markers for ALL), cytogenetics (positive for Philadelphia chromosome), polymerase chain reaction (positive for BCR::ABL1 fusion gene).
Infectious mononucleosis
SIGNS / SYMPTOMS
A self-limited condition that tends to present in young adults (high school and college students). There is generally abrupt onset of symptoms including 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
Heterophile antibody test (monospot test, positive), Epstein-Barr virus serologic test (positive), polyclonal B-lymphocyte population on flow cytometry.
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).
Reverse transcription polymerase chain reaction for HCV RNA (positive).
Cytomegalovirus infection (CMV)
SIGNS / SYMPTOMS
Immunocompromised host (e.g., post-transplant).
Cough, bone pain, visual symptoms, and diarrhea are common presenting features.
INVESTIGATIONS
CMV serology (positive), polymerase chain reaction/quantitative nucleic acid testing (positive for CMV), biopsy (positive for CMV).
Tuberculosis
SIGNS / SYMPTOMS
Not always easy to differentiate clinically, but patient may have risk factors for tuberculosis (e.g., HIV positive, history of drug use, inadequate nutrition, homelessness, poverty, crowded/insecure housing, residence in a tuberculosis-endemic country).
Cough, malaise, and weight loss are common presenting features.
INVESTIGATIONS
Chest x-ray, CT chest, purified protein derivative of tuberculin, acid-fast bacillus test, tuberculosis culture, pleural/peritoneal fluid analysis (in some cases), pleural biopsy (in some cases), bone marrow biopsy (in some cases).
HIV infection
SIGNS / SYMPTOMS
Risk factors for sexually transmitted disease (e.g., multiple sexual partners, unprotected sexual intercourse), history of intravenous drug use, multiple transfusions pre-1985, prior flu-like illness and rash.
INVESTIGATIONS
Enzyme-linked immunosorbent assay (screen), Western blot (confirm), reverse transcription polymerase chain reaction for HIV RNA (viral load) are diagnostic.
Syphilis infection
SIGNS / SYMPTOMS
Risk factors for sexually transmitted disease; prior genital chancre and rash.
INVESTIGATIONS
Treponema-nonspecific tests (rapid plasma reagin [RPR], Venereal Disease Research Laboratory [VDRL]); Treponema-specific tests, (e.g., fluorescent treponemal antibody absorption [FTA-ABS], Treponema pallidum hemagglutination assay [TPHA]) are diagnostic.
Sarcoidosis
SIGNS / SYMPTOMS
Young or middle-aged.
Cough, dyspnea, skin lesions, Bell palsy, and malaise are common presenting features. May be asymptomatic.
INVESTIGATIONS
Chest x-ray, CT chest (hilar adenopathy), bronchoscopy with biopsy of lymph nodes (noncaseating granulomas).
Rheumatoid arthritis
SIGNS / SYMPTOMS
More common in females.
Joint symptoms (pain, swelling, heat, stiffness) are characteristic features.
INVESTIGATIONS
Rheumatoid factor (positive), erythrocyte sedimentation rate (elevated), imaging (synovitis).
Systemic lupus erythematosus
SIGNS / SYMPTOMS
Much more common in females.
Characteristic features include malar rash (butterfly rash), photosensitivity, skin lesions, oral ulcers, myalgia, arthritis, and neurologic symptoms.
INVESTIGATIONS
Antinuclear antibody, anti-double-strand DNA, anti-Smith antibodies, abnormal CBC, proteinuria; American Rheumatology Association criteria for diagnosis.[79]
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