1 Which nodes are normally palpable in the healthy individual?

Out of a total of 600, only the submandibular, axillary, or inguinal nodes may at times be felt. Examiner’s skill is, of course, paramount, usually improving with time.

2 What is lymphadenopathy?

The presence of abnormal nodes, because of size, consistency, or number. Adenopathy can occur in various conditions, affecting individuals of any age, and with or without symptoms. It may be happenstance (as incidental detection by the physician or patient during routine exam) or the first sign of malignancy, the presenting manifestation of a complex systemic disorder or a self-limited finding. The differential diagnosis is always challenging.

3 How many adenopathies turn out to be “bad”?

Difficult to say, since data are scarce. In a Dutch study of 2556 patients presenting with unexplained lymph nodal enlargement to a primary care office, 10% were eventually referred to subspecialists, and 3.2% ultimately underwent biopsy. Only 29/2556 (1.1%) had a final diagnosis of malignancy. This low prevalence was confirmed by two separate U.S. studies, suggesting that the much higher neoplastic prevalence of 40–60% reported by many textbooks refers only to the 3% who underwent biopsy, thus grossly overestimating the likelihood of cancer. Hence, in primary care settings, unexplained adenopathy has a neoplastic risk of only 4% in patients 40 years or older and 0.4% in those younger than 40.

4 What is the first approach to adenopathy?

To sort out “serious” from benign. To do so, first separate generalized from localized, since these are distinct conditions with unique differential diagnoses.

5 What is a generalized adenopathy?

One that involves two or more noncontiguous sites (conversely, a localized adenopathy is one that involves only one site). Always make sure that the “localized” ones are not instead part of a generalized process. This may not be necessarily self-evident, since only 17% of all generalized adenopathies are correctly identified by primary care physicians. Hence, whenever you find an abnormal site, always evaluate all others.

6 Where should you look for enlarged nodes?

Important nodes also can be found in the popliteal fossa and paraumbilical region. Deeper ones (hilar, mediastinal, abdominal, and pelvic) are important, too, but inaccessible.

7 Which parts of the exam should be emphasized in cases of generalized adenopathy?

Those that may uncover signs of systemic disease, such as skin rash, mucous membrane lesions, hepatomegaly, splenomegaly, and arthritis.

8 What is the differential diagnosis of a generalizedadenopathy?

One of three processes: (1) a disseminated malignancy, especially hematologic (lymphomas, leukemias, and angioimmunoblastic lymphadenopathy); (2) a collagen vascular disorder (sarcoidosis, rheumatoid arthritis (RA), and systemic lupus erythematosus [SLE]); or (3) an infectious process (mononucleosis, cytomegalovirus [CMV], AIDS, toxoplasmosis, syphilis, tuberculosis, histoplasmosis, coccidioidomycosis, brucellosis, and bubonic plague). Drug reaction can do it, too, and so can intravenous abuse. Some medications (e.g., phenytoin) specifically cause lymphadenopathy; others (e.g., cephalosporins, penicillins, or sulfonamides) do it instead in the context of a serum sickness-like syndrome, with fever, arthralgias, and skin rash (see Table 18-1).

Table 18-1 Medications That May Cause Lymphadenopathy

9 Should a biopsy be done in patients with generalized lymphadenopathy?

Yes, especially considering the often serious (and systemic) character of the condition. Remember to always biopsy the largest node. If nodes are of similar size, choose in descending order: the supraclavicular, cervical, axillary, epitrochlear, and inguinal stations. The latter is the least helpful, since it often shows only reactive hyperplasia. Yet, do not disregard it. In one retrospective study (with careful patient selection), 53% of inguinal biopsies turned out to be diagnostic. Also, beware that some sites may be more prone to surgical complications than others. Sampling the parotid area, for example, can damage the facial nerve or its branches, while biopsying the posterior cervical triangle may injure the spinal accessory nerve.

10 Which is more common, localized or generalized adenopathy?

Localized. In a primary care setting, 75% of patients will present with localized involvement (head and neck, 55%; supraclavicular, 1%; axillary, 5%; inguinal, 14%).

11 Can the region of involvement narrow the diagnosis?

Yes. As in real estate, location is very important for nodes (as applied, of course, to regional or localized adenopathies). For the generalized form, differential diagnosis is another ballgame). Overall, regional adenopathy reflects localized infection or neoplasm. For instance, cat-scratch disease for cervical or axillary nodes, sexually transmitted diseases for the inguinal ones, and infectious mono for the cervical station. Finally, preauricular nodes (of any size) are usually more significant than similarly sized nodes in other locations.

12 Should one know the regions drained by the various lymphonodal stations?

Yes, since this may unlock the underlying cause. After detecting an enlarged node, always examine the region drained by it (see Table 18-2). Look for infections, skin lesions, or tumors.

Table 18-2 Lymph Node Groups: Location, Lymphatic Drainage and Selected Differential Diagnosis*

STDs = sexually transmitted diseases.

* Modified from Ferrer R: Lymphadenopathy. Am Fam Physician 58:1313–1323, 1998.

13 What are the general characteristics that can help interpret an abnormal node?

The mnemonic is ALL AGES:

14 Why does the patient’s age help?

Because it is the most important predictor of malignancy. Although lymphoproliferative disorders also may affect younger individuals, neoplastic nodes are usually more common in those older than 40 years (Table 18-3). Yet some malignant-looking nodes may actually be benign. Infectious mononucleosis, for example, may often resemble Hodgkin’s disease.

Table 18-3 Lymph Node Biopsy Findings (%)^*

15 What about associated signs and symptoms?

They can be “local” or systemic (Table 18-4). Local findings suggest infection or neoplasm in a specific site (like the swollen nodes and lymphangitic streaks of a skin infection). Conversely, systemic symptoms (such as fever, fatigue, night sweats, and unexplained weight loss) argue in favor of a collagen vascular, lymphoproliferative, or infectious disorder (e.g., tuberculosis [TB]). Still, lack of associated signs or symptoms does not exclude malignancy and thus should not stop a work-up. Finally, remember that the adenopathy of Hodgkin’s disease may become painful after alcohol ingestion.

Table 18-4 Lymphadenopathy—Associated Signs and Symptoms

* Causes of generalized lymphadenopathy.

16 What about splenomegaly?

It occurs in only 5% of adenopathies, and when it does it argues in favor of sarcoidosis, acute leukemia, chronic lymphocytic leukemia, Hodgkin/non-Hodgkin lymphoma or a mononucleosis-like syndrome. It is instead uncommon in metastatic cancer.