Castleman's disease

A case of giant lymph node hyperplasia (Castleman's disease) with an original presentation of a chylous pleural effusion occurred in a female adolescent. CT scans showed mediastinal lymphadenopathy. Lymph node biopsy was consistent with the plasmacytic variant of Castleman's disease.

(CHEST 1997; 112:1132-33)

Key words. Castleman's disease; chylous pleural effusion; giant lymph node hyperlasia

Giant lymph node hyperplasia, first described by Castleman et al[1] in 1956, occurs in two variants: hyaline vascular and plasmacytic. Each subtype has distinctive histologic features. Castleman's disease ranges from an asymptomatic, incidental localized finding on a chest radiograph to an aggressive illness with systemic symptoms and involvement. As best as can be determined, only one previous case of Castleman's disease has been associated with a chylous effusion at presentation.[2] Herein is a second case of Castleman's disease presenting with a chylous pleural effusion.

Case Report

A 13-year-old girl was admitted to the hospital with a 3-day history of fever, progressive dyspnea, and nonproductive cough. The patient had no significant prior illnesses. Noteworthy findings at the time of physical examination included a distressed, tired appearing adolescent; the temperature was 39.2 [degrees] C, and respiratory rate was 30 breaths per minute. There was dullness to percussion in both lung bases; this was greater in the left lung than in the right. Chest auscultation revealed bilateral rhonchi and end-expiratory wheezes. No murmur or rub was detected. There was no palpable hepatospienomegaly.

Physical examination otherwise disclosed no abnormalities. A chest radiograph revealed bilateral pleural effusions with nearly complete opacification of the left lung field (Fig 1). A WBC count was 31,000/[mm.sup.3], with 90% neutrophils. Diagnostic thoracentesis and therapeutic tube thoracostomy (bilateral) were performed. A follow-up radiograph demonstrated incomplete resolution of the volume loss. Pleural fluid analysis revealed thick white fluid with exudative indices (lactate dehydrogenase value, 1173 U/L [serum U/L, 697; ratio, 1.68]; protein level, 5.6 g/L [serum, 8.4 g/L; ratio, 1.5]; WBC count, 290/[mm.sup.3]; glucose, 27 mmol/L; pH, 7.05). Pleural fluid cultures were sterile. Sputum cultures grew Staphylococcus aureus. She was treated with ceftriaxone disodium. Twenty-four hours after admission, the patient became afebrile and was less distressed.

Serial chest radiographs showed persistent densities and a CT scan of the chest was performed. The CT scan demonstrated bilateral loculated effusions with more extensive disease in the left hemithorax. An anterior mediastinal inflammatory mass effect was apparent. A decortication procedure performed via a left posterior lateral thoracotomy revealed a dense, white rind encasing the entire left lung. Pleural fluid obtained at the time of this procedure revealed a triglyceride level of 403 mg/dL and a cholesterol level of 50 mg/dL.

The patient continued to have large output through the chest tube and was subsequently kept from any oral intake. A Gastrografin (diatrizoate meglumine) swallow performed to rule out an esophageal injury was negative. A subsequent pleural fluid analysis revealed an increased cholesterol level and chylomicrons. Chest tube drainage decreased while the patient was receiving nothing orally and parenteral hyperalimentation, but increased when enteral feedings were resumed. Another CT scan of the Chest showed increased anterior mediastinal adenopathy. A left anterior mediastinotomy was performed for tissue diagnosis. The tissue specimen was consistent with the plasmacytic variant of giant lymph node hyperplasia (Castleman's disease [Fig 2]). This diagnosis was confirmed by a second pathologic review.

The patient's postoperative course was complicated by ARDS requiring prolonged mechanical ventilatory support. She eventually was weaned from the ventilator and was discharged home in satisfactory condition. She remains stable 2 years later, though she does have a moderately severe restrictive lung disease as a result of intrathoracic fibrosis.

The patient's latest pulmonary function tests showed the following: [FEV.sub.1] 1.17 L (44% of predicted value); FVC, 1.39 L (44% of predicted value); total lung capacity, 1.88 L (40% of predicted value); and diffusion capacity, 13.3 mL/min/mm Hg (50% of predicted value). Arterial blood gas values were as folllows: pH, 7.44; [Pco.sub.2], 39 mm Hg; [Po.sub.2], 94 mm Hg; and arterial oxygen saturation, 98%. Although she has required no further treatment, she is being followed up closely because of the high risk of malignant degeneration.

Discussion

Giant lymph node hyperplasia was first described by Castleman et al[1] in 1956. Keller et al[3] described two distinct histologic variants: plasmacytic and hyaline vascular. Rarely, a mixed histologic pattern with characteristics of both subtypes is found. Clinical presentations range from benign incidental radiographic findings to an aggressive, systemic disease.

The hyaline-vascular variant is characterized histologically by the onion-skin appearance of small lymphocytes circumferentially surrounding lymph node follicles. in addition, the germinal centers display a prominent vascular interfollicular stroma and frequently contain deposits of hyaline material. The plasmacytic variant displays sheets of mature plasma cells in the interfollicular zone and has a less vascular stroma.[3]

The clinical presentations of the two variants are disparate. The hyaline-vascular variant is more common, occurring in a ratio of 10:1. While patients with the hyaline-vascular variant may present with local symptoms, such as an enlarging painless mass or sequelae of upper airway compression, most patients are asymptomatic. The median age at presentation is 23.5 years for patients with localized disease., Complete surgical excision is the primary modality of therapy with radiation therapy reserved for rare unresectable cases. In contrast to the benign course of most cases of the common hyaline-vascular variant of Castleman's disease, the plasmacytic variant tends to be more aggressive. The plasmacytic variants commonly involve multiple lymph node sites while single lymph node involvement is typical of the hyaline-vascular group. Multicentric disease is most commonly seen with the hyaline-vascular subtype, though it has been described with the plasmacytic subtype. Patients with multicentric disease tend to be older (median age, 56 years).[4] Multicentric disease is associated with "B" symptoms including fever and night sweats. Common laboratory abnormalities include anemia, hyperglobulinemia, hypoalbuminemia, and an elevated sedimentation rate. Multicentric disease may be very aggressive and may require systemic chemotherapy. Despite aggressive treatment, the median survival time for multicentric disease is 26 months, compared with a nearly 100% 5-year survival with localized hyaline vascular lymph node hyperplasia.[5]

Both pleural and pericardial effusions have been described at presentation of Castleman's disease, but as far as is known, there has been no report of a chylous effusion as an original presentation of Castleman's disease.[6,7] The most probable pathogenesis of the chylous effusion in the patient reported herein was a local lymphatic compression with impaired drainage into the thoracic duct, although alternative mechanisms are possible.

Conclusion

Castleman's disease is an uncommon illness that can present with a variety of symptoms. Castleman's disease should be considered in patients with mediastinal adenopathy or chylous effusions, or both.

References

[1] Castleman B. Iverson L, Menendez V. Localized mediastinal lymph-node hyperplasia resembling thymoma. Cancer 1956; 9:822-30

[2] Toyoshima T, Sezai S, Marumo K, et al. A case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia associated with pleural and peritoneal chylous effusion. Nippon Naika Gakkai Zasshi 1989; 78:1795-96

[3] Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 1972; 29:670-83

[4] Shahidi H, Myers JL, Kvale PA. Castleman's disease. Mayo Clin Proc 1995; 70:969-77

[5] Weisenburger DD, Nathwani BN, Winberg CD, et al. Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases. Hum Pathol 1985; 16:162-72

[6] Reynolds SP, Gibbs AR, Weeks R, et al. Massive pleural effusion: an unusual presentation of Castleman's disease. Eur Respir J 1992; 5:1150-53

[7] Nicolosi AC, Almassi GH, Komorowski R. Cardiac tamponade secondary to giant lymph node hyperplasia. Chest 1994; 105:637-39

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