Predictors of Malignancy in Lymphadenopathy—To Biopsy or Not to Biopsy?

Abstract & Commentary

Synopsis: The risk of finding malignancy in an enlarged lymph node increased with increasing size and number of sites of adenopathy and increasing age. Other significant predictors of malignancy were a supraclavicular location, an abnormal chest X-ray, and fixed nodes.

Source: Soldes OS, et al. Predictors of malignancy in childhood peripheral lymphadenopathy. J Pediatr Surg 1999;34: 1447-1452.

Soldes and associates from the c.s. mott children’s Hospital in Ann Arbor reviewed the medical records of 60 consecutive patients younger than 18 years of age who underwent surgical procedures for peripheral lymphadenopathy between January 1991 and December 1993. Data concerning physical findings, history of illness, laboratory and radiological evaluation, and pathological diagnosis were abstracted from the records. Information included the anatomic location; the size in centimeters; the presence of fever, cough, tenderness, and skin involvement; and whether the node was fixed to surrounding tissue or fluctuant. Historical information included the duration of lymphadenopathy, a history of malignancy or immunodeficiency, recent antibiotic therapy, and exposure to animals or to tuberculosis. Laboratory and radiological studies done before the surgical intervention were noted. Multivariate logistic analysis was applied to determine the significant risk factors predicting malignancy in these children with lymphadenopathy.

Malignant lymphadenopathy, chiefly Hodgkin’s disease and lymphoma, was diagnosed in 16 patients (27%); 44 (73%) of the nodes were benign. Of the benign nodes, 16 (27%) had an infectious etiology, chiefly streptococcal and staphylococcal abscesses. Nearly half of the infectious lymph nodes were fluctuant and fluctuance was associated with benignity. Four children had Mycobacterium avium intracellulare lymphadenopathy. We used to call these "atypical acidfast" lymphadenopathies. Twenty-one lymph nodes (35%) were defined as "probably infectious," showing reactive hyperplasia or granulomatous inflammation and negative cultures.

Factors associated with a relatively high risk of malignancy were supraclavicular location, an abnormal chest X-ray, and fixed lymph nodes. Variables such as duration of lymphadenopathy, fever, cough splenomegaly, and tenderness did not help differentiate benign from malignant nodes.

Comment by Howard A. Pearson, MD, FAAP

An enlarged lymph node, particularly one that is visible and persistent, often evokes a great deal of anxiety about the possibility of malignancy. For years we have been wary of nodes in certain anatomic locations, such as supraclavicular and posterior cervical regions. We are also concerned if the nodes are hard, nontender, or fixed to surrounding tissues. The study by Soldes et al attempts to develop a multivariate scoring system to help decide whether a specific enlarged lymph node warrants biopsy. It also supports previous studies that most of these enlarged nodes are not malignant. Factors increasing the possibility of malignancy include older age, larger size, and multiple sites (although not bilateral, symmetrical nodes such as bilateral anterior cervicle nodes). Two of their statistically significant factors for malignancy were a supraclavicular location and an abnormal chest roentgenogram. These are probably related because of the continuity of supraclavicular lymph nodes with the anterior mediastinum—the usual location of Hodgkin’s disease and other lymphomas. It is also fairly obvious that new lymphadenopathy in a child with a history of malignancy requires prompt definition, not only because a significant risk of recurrence but also because of the usual family anxiety. Soldes et al’s list of characteristics of probably benign lymphadenopathy includes especially fluctuance. Several factors were not found to be useful in differentiating benign vs. malignant lymph nodes, including duration of the lymphadenopathy, presurgical antibiotic use, fever, cough, splenomegaly, node tenderness, or skin involvement (erythema, induration).

Soldes et al conclude that older children (> 8 years of age) with an enlarged lymph node of supraclavicular location and/or those who have an abnormal chest X-ray should undergo prompt biopsy. In contrast, younger children with a small single node in one location have a low risk of malignancy and may be managed by further testing including tuberculin skin test, chest X-rays, and consideration of a course of antibiotics.

Immediate surgical biopsy of an enlarged lymph node should be strongly considered for all of the following except:

a. the node is located in the supraclavicular area.

b. the presence of other large lymph nodes.

c. induration and redness of the overlying skin.

d. the presence of an abnormal chest x-ray.