L-23 Lymph Nodes, Lymphadenitis and Lymphadenopathy

• Lymph nodes filter lymph and help activate the immune system
• Lymphadenitis is a lymph node infection causing an inflammatory reaction
• Lymphadenopathy is the hyperplasia of lymph nodes for known or unknown reasons, including inflammation, infection, or malignancy.
• Peripheral lymph nodes can be located in superficial cervical, posterior and deep cervical, preauricular, postauricular, suboccipital, tonsillar, submandibular, submental, supraclavicular, axillary, epitrochlear, inguinal, or popliteal areas.
• Localized lymphadenopathy suggests local causes.
• Generalized lymphadenopathy is usually a manifestation of a systemic disease.
• Lymph node characteristics include size, tenderness, mobility, fluctuance, consistency, temperature, and erythema.
• 75% of Lymphadenopathy is localized and 25% is generalized

Subjective Chief Complaint

• "I have bumps on my neck" is a possible chief complaint

HPI (History of Present Illness) Example

• A 66-year-old male noticed "bumps" on the lateral/anterior aspect of his neck for about 5-6 weeks.
• The patient noticed the "bumps" while shaving and thought they would go away.
• The patient is unsure if the bumps are getting bigger but they are certainly not going away.
• The bumps are not painful, even when pressed on.
• The patient has not noticed any other areas with bumps.
• The patient reports nothing makes the bumps better or worse
• The patient has been a little more tired lately but reports no fever or weight loss
• The patient is worried the bumps are not going away and thinks it could be cancer.

ROS (Review of Systems) Summary

• General: no chills or malaise
• HEENT: no rhinorrhea, sore throat, dry eyes, or dry mouth
• Heart: no chest pain, palpitations, or syncope
• Pulmonary: no dyspnea, orthopnea, or wheezing
• Abdominal: no nausea, vomiting, pain, swelling, blood in stools, or tarry stools
• GU: no dysuria, frequency, penile discharge, or genital lesions
• Extremities: no edema or joint pain
• Musculoskeletal: no muscle weakness, joint stiffness, joint pain, numbness, or tingling
• Skin: No rashes, no bruising
• Psychiatric: denies anxiety or depression.

PMH (Past Medical History) Summary

• The patient had mono when they were 16 years old
• No adult illnesses
• The patient thinks they are up to date with vaccinations
• No past surgeries
• Does not take any prescription or over the counter medications, vitamins or supplements
• No allergies
• Mother has high blood pressure and rheumatoid arthritis and is 85 years old
• Father died from a heart attack when he was 65yo
• No brothers or sisters
• Has one daughter, who is 11 years old and healthy

Social History (SH) Summary

• Owns a lawn service company
• Not directly working with herbicides, fertilizers, and other chemicals for the last year
• Worked directly with chemicals for about 20 years
• Used to smoke cigarettes at one pack a day for about 10 years and stopped about 20 years ago
• Drinks alcohol socially
• Smoked marijuana sometimes as a teenager

Additional History

• Daughter has a cat and a rabbit
• Not hobbies that involves animals like hunting
• Diet consists of vegetables, fruits, steak, chicken, rice, bread and pasta
• Does not eat any undercooked meats, likes his steaks cooked medium-well
• No recent travel
• Gets mosquito bites a lot
• About ten sexual partners in the last year
• Usually prefers females
• Was treated for syphilis a couple of years ago and chlamydia and gonorrhea before that
• Sometimes uses condoms
• Sometimes gives oral sex

Important History Questions for Lymphadenopathy

• Timing: changes in lymph nodes since they were first noticed, including size, pain, consistency, and mobility
• Constitutional symptoms: fever, night sweats, weight loss, or fatigue, which may suggest lymphoma, tuberculosis, collagen vascular diseases, unrecognized infection, or malignancy
• Symptoms in areas that drain to the enlarged lymph nodes: localizing signs or symptoms
• Past medical history: previous cancers, prior radiation or chemotherapy treatments, infections (EBV mononucleosis, HIV, hepatitis B or C), autoimmune disease (SLE, RA), and medication use
• Social history: occupation, hobbies, and risky behaviors can help narrow down the differential diagnosis because exposures during these activities can help determine the possible cause of the lymphadenopathy

Differential Diagnosis (Mnemonic: MIAMI)

• Malignancies: lymphomas, leukemias, Kaposi sarcoma, metastases, melanoma
• Infections:
  • Bacterial: brucellosis, cat-scratch disease (Bartonella), chancroid, cutaneous infections (staphylococcal or streptococcal), lymphogranuloma venereum, primary and secondary syphilis, tuberculosis, tularemia, typhoid fever
  • Granulomatous: berylliosis, coccidioidomycosis, cryptococcosis, histoplasmosis, silicosis
  • Viral: infectious mononucleosis (Epstein-Barr virus), adenovirus, cytomegalovirus, hepatitis, herpes zoster, human immunodeficiency virus (HIV), rubella
  • Other: fungal, helminthic, Lyme disease, rickettsial, scrub typhus, toxoplasmosis
• Autoimmune disorders: dermatomyositis, rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus (SLE)
• Miscellaneous/unusual conditions: angiofollicular lymph node hyperplasia (Castleman disease), histiocytosis, Kawasaki disease, Kikuchi lymphadenitis, Kimura disease, sarcoidosis
• Iatrogenic causes: medications such as phenytoin, allopurinol, captopril, atenolol, and others; serum sickness caused by penicillin, cephalosporins

Physical Exam (PE) Example

• Vitals: temp 98.6°F, pulse 84 regular, RR 14, BP 128/78mmHg, 185lbs, 68in, BMI 28.1
• General: alert and oriented, in no acute distress
• HEENT: TM's pearly grey and intact, no nasal discharge, good dentition, tonsils not enlarged, pharynx no erythema or suppuration, no tongue or buccal masses
• Neck: supple, no thyromegaly, 2 right superficial cervical lymph nodes 2cm each firm, non-tender, and fixed, multiple left superficial cervical lymph nodes 1cm firm, non-tender, and fixed, multiple bilateral posterior cervical lymph nodes 1cm firm, non-tender, mobile, no palpable occipital, postauricular, preauricular, tonsillar, submental, submandibular, or deep cervical lymph nodes bilaterally
• Heart: S1 S2 without murmurs or rubs
• Pulmonary: CTA bilaterally
• Abdominal: no lesions, round, positive bowel sounds, no masses, no rebound, no tenderness, no hepatosplenomegaly
• Genitalia: patient declines
• Lymphatic: multiple <1cm soft, non-tender, movable bilateral axillary and inguinal lymph nodes present, no palpable supraclavicular, epitrochlear or popliteal lymph nodes bilaterally
• Extremities: no clubbing, no edema, no cyanosis
• Skin: no rashes, no lesions

Lymph Node Regions and Drainage

• Preauricular nodes drain scalp and skin and differential diagnosis includes scalp infections, mycobacterial infection and malignancies such as skin neoplasm, lymphomas, head and neck squamous cell carcinomas
• Posterior cervical nodes drain scalp, neck, and upper thoracic skin. Differential diagnosis is same as preauricular nodes.
• Submandibular nodes drain oral cavity and differential diagnosis includes mononucleosis, upper respiratory infection, mycobacterial infection, toxoplasma, cytomegalovirus, dental disease, rubella and malignancies such as squamous cell carcinoma of the head and neck, lymphomas, and leukemias
• Anterior cervical nodes drain larynx, tongue, oropharynx, and anterior neck and differential diagnosis is same as submandibular nodes
• Supraclavicular nodes drain gastrointestinal tract, genitourinary tract, pulmonary and differential diagnosis includes thyroid/laryngeal disease, mycobacterial/fungal infections and malignancies of the abdominal/thoracic
• Axillary nodes drain breast, upper extremity, thoracic wall and differential diagnosis includes skin infections/trauma, cat-scratch disease, tularemia, sporotrichosis, sarcoidosis, syphilis, leprosy, brucellosis, leishmaniasis and malignancies such as breast adenocarcinomas, skin neoplasms, lymphomas, leukemias, soft tissue/Kaposi sarcoma
• Infraclavicular nodes differential diagnosis includes Highly suspicious for non-Hodgkin lymphoma
• Epitrochlear nodes drain ulnar forearm, hand and differential diagnosis includes Skin infections, lymphomas, and skin malignancies
• Horizontal node group and vertical node group drain lower abdomen, external genitalia (skin), anal canal, lower one-third of vagina, lower extremity and differential diagnosis includes Benign reactive lymphadenopathy, sexually transmitted diseases, skin infections and malignancies such as Lymphomas; squamous cell carcinoma of penis, vulva, and anus; skin neoplasms; soft tissue/Kaposi sarcoma
• Left supraclavicular nodes drain gastrointestinal, abdominal, thoracic, or retroperitoneal cancers and lymphoma
• Virchow's node is the left supraclavicular node and drains the left head, neck, chest, abdomen, pelvis, and bilateral lower extremities.

Additional Physical Exam Information

• Complete physical exam, examine all accessible lymph nodes paying attention to location, size, consistency, and tenderness.
• Supraclavicular lymphadenopathy is almost always abnormal
• Right supraclavicular lymph nodes drain parts of the lung and mediastinum
• Left supraclavicular lymph nodes also known as Virchow's nodes drain intra-abdominal regions and parts of the thorax
• Skin exam looking for lesions, erythema, or trauma
• In HEENT exam, check mouth, under tongue palpation for masses or ulcers
• Heart: listen for muffled heart sounds could indicate mediastinal masses, pericardial effusions
• Lungs: auscultate all fields for decreased breath sounds
• Abdomen: check for hepatosplenomegaly (HSM), masses, tenderness
• Neurologic exam for any deficits

Lymph Node Characteristics (Normal)

• Size: generally <1.0 cm (10mm), inguinal <1.5cm (15mm), and supraclavicular, epitrochlear or popliteal <0.5cm (5mm)
• Consistency: usually soft
• Fixation: freely movable in the subcutaneous space
• Tenderness: usually non-tender

Lymph Node Characteristics (Abnormal)

• Size: most lymph nodes >1.0 cm (10mm), inguinal >1.5cm (15mm), and supraclavicular, epitrochlear or popliteal >0.5cm (5mm)
• Consistency: Hard nodes are found in cancers that induce fibrosis. Firm, rubbery nodes are found in lymphomas and chronic leukemia.
• Fixation: fixed to adjacent tissues or can also become fixed to each other ("matted")
• Tenderness: usually non-tender in neoplasia, but may be tender with some inflammatory processes (infectious, hemorrhage into node, inflammatory stimulation, malignancy)

Diagnostic Testing

• Should be tailored depending on findings on history and physical exam
• Consider whether lymphadenopathy is localized or generalized
• Specific patient characteristics: age, occupation, environmental exposures, etc.
• CBC with differential to check for infection, leukemia, anemia
• CMP (LFT's)
• Calcium level (elevated in malignancies)
• Lactate dehydrogenase (LDH) (elevated in malignancies)
• Uric acid (elevated in malignancies)
• Specific tests:
  • Heterophile antibody (EBV), IgM for CMV or toxoplasmosis, PPD or quantiferon for tuberculosis (Tb)
  • RPR with FTA-ABS for syphilis, HIV test
  • Anti-nuclear antibody (ANA), rheumatoid factor (RF) and others for autoimmune disorders

Diagnostic Testing (Imaging)

• Helps define node size and distribution of lymph nodes more precisely
• Evaluates surrounding structures for abnormalities
• Is not a substitute for a biopsy
• Ultrasound: may help differentiate cystic from solid masses
• Doppler technology to check for blood flow
• Specific imaging studies:
  • Chest X-ray (CXR)
  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Positron emission tomography (PET)

Diagnostic Testing (Lymph Node Biopsy)

• Mode of biopsy will depend on where the lymphadenopathy is located and the suspected diagnosis
• Open biopsy or excisional biopsy: examination of intact tissue with assessment of abnormal cells and abnormal node architecture, select most abnormal, suspicious, and accessible node, fixed and unfixed tissue is needed, definitive diagnosis in non-Hodgkin lymphoma including specific information necessary for treatment
• Core needle biopsy: provides tissue for special studies and some information on nodal architecture, relatively low-morbidity procedure and an inexpensive alternative to open biopsy in select patients
• Fine-needle aspiration for cytology: most useful when searching for recurrence of cancer, false-positive results are uncommon, and there is false-negative results because of sampling errors, quick and minimally invasive, no information on tissue architecture

Diagnosis: Non-Hodgkin Lymphoma

• History: enlarging cervical lymphadenopathy, EBV infection history, occupational environmental exposures, high risk behavior, presence of constitutional symptoms such as fever, night sweats, and fatigue, "B" symptoms consisting of fever >100.4°F, drenching night sweats, and unexplained weight loss of >10% of body weight over the past six months
• Physical Exam: suspicious lymph node characteristics of fixed, non-tender, and firm; assessed all accessible lymph nodes showing generalized lymphadenopathy without abdominal masses or organomegaly and no skin abnormalities
• Testing: CBC normochromic normocytic anemia, mild thrombocytopenia, LDH elevated, HIV test positive, RPR 1:1, FTA-ABS positive
• Excisional lymph node biopsy (gold standard): large, transformed B cells with prominent nucleoli and basophilic cytoplasm consistent with non-Hodgkin lymphoma.

Differential Diagnosis Considerations

• Human immunodeficiency virus (HIV) history of cervical lymph nodes, fever, night sweats, multiple sexual partners, history of sexually transmitted infections, generalized lymphadenopathy, positive HIV diagnostic testing
• Rheumatoid Arthritis history of cervical lymph nodes, fever, family history of rheumatoid arthritis
• Oropharyngeal cancer history of cervical lymph nodes, night sweats, multiple sexual partners including oral sex, history of sexually transmitted infections, history of tobacco use generalized lymphadenopathy; HPV-associated oropharyngeal cancers are primarily found in the oropharynx, base of the tongue, and tonsil