Solitary Lymphadenopathy

Daryl Lum, M.D. and Steven Applebaum, M.D.

Case Report

A 42-year-old male presented for a routine physical examination, with his last examination occurring approximately 1 year earlier. He reported an upper respiratory infection approximately 1 month earlier and had noticed some slight left neck swelling in the shower. His upper respiratory infection symptoms had resolved completely and he denied any fevers, chills, night sweats, or weight loss. The patient's past medical history was significant for a history of hemorrhoids and a penile vein ligation following a groin injury. The patient took no medications and had not had any recent travel. He had previously smoked 5 cigarettes per day for approximately 10 years, but had quit approximately 10 years earlier.

On physical examination, the patient was a well-appearing male. Blood pressure was 112/80 mm Hg, pulse 84 beats per minute, and temperature 98.4°F. Head and neck examination was remarkable for an approximately 5 mm soft, supraclavicular lymph node. The pulmonary and respiratory examinations were normal and the abdominal examination showed no masses, normal bowel sounds, and no hepatosplenomegaly. There was no other peripheral lymphadenopathy appreciated. Laboratory tests revealed a white blood cell count of 8.41, hemoglobin 12.4, platelets 322, lactate dehydrogenase 158, and a normal comprehensive metabolic panel.

Chest radiograph showed no evidence of lymphadenopathy and a fine needle aspiration (FNA) was performed that day. The FNA showed some atypical cells and a possible Reed Sternberg cell. The patient was subsequently referred for an excisional biopsy. A computed tomographic (CT) scan of the chest revealed left supraclavicular and mediastinal lymphadenopathy, with the largest node within the mediastinum measuring 1.6 cm. A CT scan of the abdomen and pelvis showed no lymphadenopathy, a normal liver and spleen, and sigmoid diverticulosis. The patient's biopsy was consistent with nodular sclerosing Hodgkin's lymphoma and he was classified as Stage IIA disease. He was treated with 4 cycles of chemotherapy using the drug combination of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), followed by external beam radiation therapy. It has been approximately 1 year past his initial diagnosis and his most recent positron emission tomographic scan shows no evidence of disease.

Discussion

Lymphadenopathy is often encountered on physical examination and the majority of causes are benign or self-limited. The prevalence of malignancy is low with one study demonstrating a 1.1% prevalence of malignancy in patients presenting with unexplained lymphadenopathy.¹ The prevalence of malignancy increases with increasing age. A careful history and physical examination should be performed in all patients who present with lymphadenopathy. A history of tobacco use has particular significance in this setting, as the potential for smoking-related lung or head and neck cancer will heighten one's attention. Medications that are associated with lymphadenopathy include allopurinol, atenolol, captopril, carbemazepine, gold, hydralazine, phenytoin, primidone, quinidine, and trimethoprimsulfamethoxazole. Lymph nodes that are hard and fixed should raise one's suspicion for malignancy, while firm, rubbery nodes are seen in lymphoma. The pattern and location of lymphadenopathy should also raise one's suspicion for malignancy. Cervical lymphadenopathy is commonly found in adults and is often related to a viral infection; however, the presence of supraclavicular lymphadenopathy is often associated with malignancy, with 54% to 85% of biopsies showing malignancy in various series.

Fine needle aspiration has become a useful tool in evaluating a number of conditions because it is fast, safe, and cost effective. Typically, on-site evaluation of the aspirated specimen is performed to assess adequacy of sampling and to perform additional sampling if necessary. Previously, there were concerns that FNA was not useful in evaluating lymphadenopathy because it was felt that not enough tissue was obtained; however, studies have demonstrated its effectiveness in evaluating supraclavicular lymphadenopathy. The sensitivity of FNA has also been greatly enhanced with the increasing number of immunohistochemical stains available to aid the pathologist interpreting the specimen. One study involving 218 cases of supraclavicular lymphadenopathy demonstrated a sensitivity of 92.7%, specificity of 98.5%, predictive value positive of 97.3%, and negative predictive value of 94.8%.²

Another study also demonstrated the utility of FNA. In this study of 309 aspirates of supraclavicular lymphadenopathy, 55% showed malignancy (47% metastatic and 8% lymphoma). In this study, age was associated with a higher risk of malignancy, with 68% of cases occurring in patients older than 40 years and 32% occurring in patients 40 years or younger. In the younger patients diagnosed with malignancy, lymphoma occurred more often than metastases (lymphoma to metastatic ratio was 1:1.6 in patients 40 years or younger, and 1:11 in patients older than 40 years). Hodgkin's was the most common type of lymphoma diagnosed, representing 40% of the cases that were diagnosed. There were also racial differences noted in this study with lymphoma occurring twice as frequently in Caucasians when compared to other ethnicities.³

Hodgkin's lymphoma has an incidence of approximately 3 cases per 100,000 per year. It occurs more frequently in males and has a bimodal peak in incidence. There are 5 subtypes of Hodgkin's lymphoma: nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, and unclassifiable. Nodular sclerosing type accounts for approximately 80% of cases and tends to occur in younger patients. Patients are stratified according to stage and the presence or absence of B symptoms (fever greater than 100.4°F, drenching night sweats, or greater than 10% loss of body weight). The overall prognosis for a patient with stage IIA disease treated with ABVD chemotherapy and radiation is 95%.

The finding of peripheral lymphadenopathy is often encountered by primary care physicians and has a number of causes. In addition to performing a thorough history and physical examination, an increased suspicion for malignancy should be raised in patients with a prior history of malignancy, age older than 40 years, and hard lymph nodes. In addition, supraclavicular lymphadenopathy has been associated with a higher incidence of malignancy. In the case described above, the patient had no symptoms, despite having stage IIA Hodgkin's lymphoma.

Fine needle aspiration is an effective way of evaluating peripheral lymphadenopathy with a high degree of sensitivity and specificity, and newer immunohistochemistry stains have improved the sensitivity in diagnosing malignancies which may have been missed in the past. Still, if lymphadenopathy persists or worsens in a patient with a non-diagnostic biopsy, the patient should be referred for an excisional biopsy. This case also illustrates the speed in which one can achieve a diagnosis using FNA. The patient in this case had an FNA performed during his initial office visit, and had a diagnosis of probable Hodgkin's disease within 48 hours. Clearly, the finding of the adenopathy before development of symptoms, and thus the diagnosis at an early stage will greatly improve this patient's likelihood of long-term survival.