Background & Definitions
- There are ~600 lymph nodes in the body!
- Only submandibular, cervical, axillary and (rarely) inguinal nodes MAY be palpable in healthy adults
- Lymphadenopathy (LAD) refers to nodes that are abnormal in either size (normal <1 cm diameter in adults), consistency, or number
- Supraclavicular, popliteal, and epitrochlear nodes >0.5 cm are abnormal; some say inguinal nodes >1.5-2 cm
- Hard, matted lymph nodes are abnormal
- Classified as generalized if enlarged in 2 or more noncontiguous regions or localized if only 1 region
- In primary care patients with LAD, 75% of patients present with localized and 25% with generalized LAD
Etiologies
There are lots of possibilities, but “MIAMI” can help us remember.
What is the incidence of malignancy in unexplained LAD in primary care patients?
A 1988 retrospective Dutch study estimates the incidence of unexplained LAD in the general population as well as the sensitivity and specificity of PCP referral for suspicion of malignancy after initial evaluation.
- Coding data used to estimate a 0.6% incidence of unexplained LAD in the Dutch population
- The authors extrapolated a total estimated 2,556 patients in their population over 3 years of study would have presented with unexplained LAD
- Of 2,556 patients, based on examination of all lymph node histologic/cytologic exams from 1982-1984 in the hospital of Maastricht, 3.2% (82) required biopsy, and only 1.1% (29) had a malignancy
- Early PCP referral (within 4 wks) for suspicion of malignancy was 90% sensitive, 98% specific
Two case series from primary care in the United States support this incidence and low prevalence of malignancy – 0 of 80 patients and 3 of 238 patients with unexplained lymphadenopathy were diagnosed with malignancy.
In contrast, the prevalence of malignancy in lymph node biopsies performed in referral centers is 40-60%, a statistic frequently cited in many textbooks. This overestimates the probability of malignancy in patients with LAD in the primary care population because they exclude the 97% of patients with LAD who do not undergo biopsy.
Characterizing LAD
In patients with LAD, always consider the following:
- Patient age and medical history
- Size and number
- Localized vs generalized
- Quality of the node(s)
- Time course and progression
- Associated symptoms & exposures
Age, size, and number:
Normal lymph node size varies with age, as do the most common diagnoses.
Age over 40yo is associated with higher likelihood of malignancy.
- Fijten estimates patients >40yo with unexplained LAD carry ~4% risk of cancer versus 0.4% in younger patients (except those with supraclavicular LAD)
Lymph nodes generally are not palpable in newborns. With time and antigenic exposure, volume of lymph node tissue increases.
Palpable cervical, axillary, and inguinal lymph nodes can be normal in children.
“Shotty” LAD describes the finding of small mobile lymph nodes – very common in young children and generally benign.
In a series of children younger than 5 years of age, 44% had palpable lymph nodes at the time of a routine visit, and 64% of children seen for sick visits had palpable lymph nodes.
In a study that aimed to identify factors associated with malignant etiologies of childhood peripheral LAD, useful physical findings for differentiating malignant from benign LAD in pediatric patients included the following (noting that the study only included biopsied nodes):
- Age
- Larger node size
- Location: supraclavicular LAD most likely to be malignant (75% vs 22% for all other sites)
- Fixed nodes
- Abnormal CXR
Findings with no significant difference in the above study:
- Bilateral vs unilateral
- Duration of adenopathy
- Associated symptoms (fever, splenomegaly, skin involvement, nodal tenderness)
- Leukocytosis
Location, Location, Location:
Remember that only submandibular, cervical, axillary and (rarely) inguinal nodes MAY be palpable in healthy adults. Palpation of other nodes can suggest an array of possible underlying issues.
Another summary table from Pediatrics in Review: 
Localized vs Generalized:
Remember that LAD is classified as generalized if LAD appears in 2 or more noncontiguous regions or localized if only 1 region.
- Kikuchi disease, also called Kikuchi-Fujimoto disease or Kikuchi histiocytic necrotizing lymphadenitis, was originally described in young women and is a rare, benign condition of unknown cause usually characterized by cervical lymphadenopathy and fever.
Node quality:
Time course:
Associated symptoms and exposures:
Additional pearls:
- Lymphangitic streaking suggests cutaneous infection
- Splenomegaly is rare with LAD and suggests infectious mononucleosis, lymphoma, CLL, or some acute leukemias
- Constitutional symptoms (fever, fatigue, malaise) are generally not helpful but can be see in mononucleosis
- Fevers >38ºC, drenching night sweats, weight loss >10% body weight are present in 8% of patients with Stage I Hodgkin’s disease and 68% of patients with Stave IV, and 10% of patients with non-Hodgkin’s lymphoma
- Generalized pruritis concomitant with appearance of LAD raises concern for lymphoma – present in 35% with Hodgkin’s and 10% with non-Hodgkin’s lymphoma; some consider a positive predicting factor for the need for node biopsy
Take-Home Points!
- The incidence of malignancy in patients with unexplained LAD in primary care is low
- When the cause is unknown, classify as localized or generalized
- Localized should be evaluated for etiologies according to region
- Generalized LAD suggests underlying systemic disease, requiring further investigation
- Classic risk factors for malignancy include male sex (2.72 RR, one study only, not in primary care), age older than 40 years, supraclavicular location, fixed or very large nodes, and presence of systemic symptoms
- Work-up may include labs, imaging, and biopsy depending on clinical presentation, although for localized lymphadenopathy without risk factors a reasonable course is to observe for one month
Blog post based on Med-Peds Forum talk by Chelsea Boyd, PGY3