Pathological Case of the Month FREE

Figure 1. Thoracoscopic view of parietal pleura overlying right ribs. Note granulomas studding pleura, including 2 larger outgrowths seen in center (original magnification ×8).

Figure 2. Thoracoscopic view of visceral pleura adhesed to parietal pleura at lung apex. Collapsed right lung (secondary to selective left-lung ventilation during procedure) seen at base of photograph. Granulomas are noted diffusely over the parietal pleura. Granulomas on visceral pleura are not as prominent because that pleural surface is collapsed against right lung (original magnification ×8).

Figure 3. Diffuse chronic inflammation and granulomas with multinucleated giant-cell formation in pleural tissue (hematoxylin-eosin, original magnification ×200).

Pleural effusions can be divided into transudative and exudative processes. The fluid-serum ratio of protein is less than or equal to 0.5 for a transudate and greater than 0.5 for an exudate; the fluid-serum ratio for LDH is less than or equal to 0.6 for a transudate and greater than 0.6 for an exudate.¹ Other than tuberculosis (TB), possible infectious causes to exudative pleural effusions include pneumonias stemming from bacteria such as Staphylococcus aureus, group A streptococcus, Haemophilus influenzae type b, and Mycoplasma pneumoniae; viruses such as cytomegalovirus, herpes simplex virus, or influenza; or fungi such as Blastomyces dermatitidis and Coccidioides immitis. Noninfectious causes include malignancy, chylothorax, lymphangiectasia, uremia, infarction of either the heart or lung, collagen-vascular diseases, and drug reactions. Despite findings reported by earlier researchers, more recent large case series of tuberculous pleural effusion suggest that glucose in the pleural fluid can be variable.²

Definitive diagnosis of tuberculous pleural effusion requires analysis of multiple samples with mycobacterial stain and culture. The most sensitive culture material is the pleura itself, which demonstrates caseating granulomas in up to 90% of cases and positive culture findings in up to 70%, but only rarely shows acid-fast bacilli on stain. Acid-fast bacilli stain of pleural fluid is likewise usually negative, and pleural fluid cultures are only positive for Mycobacterium tuberculosis in 30% to 50% of cases.³ In our patient, only the pleural tissue culture became positive for M tuberculosis 35 days into incubation. Ancillary biochemical tests such as adenosine deaminase and interferon-γ levels in the pleural fluid can be used as adjuncts in diagnosis.² For patients with a clinical presentation compatible with tuberculous pleural effusion, positive PPD findings, and pleural biopsy results showing granulomatous inflammation, TB is virtually certain, and therapy is usually begun with 3 to 4 antituberculous medications.² Our patient received isoniazid, rifampin, pyrazinamide, and ethambutol before the culture results were available.

Tuberculous pleural effusion can be a manifestation of either primary or reactivation disease.² This patient had negative PPD results on arrival to the United States, but her PPD was positive at 22 mm within 48 hours of this admission. One would suspect that TB manifesting 4 months after emigration resulted from primary infection in the country of origin. Tuberculous pleural effusion is thought to represent a delayed hypersensitivity response to mycobacterial antigens in the pleural space, which gain access via rupture of subpleural caseous foci.⁴The low organism burden nevertheless gives rise to the presence of an immunologically mediated effusion that causes most symptoms seen in these patients.² Left untreated, tuberculous pleural effusion usually resolves spontaneously but later returns as active TB. In a series of 141 military personnel with serofibrinous pleural effusions and positive PPD findings, 92 (65%) subsequently developed some form of active TB, although most had originally resorbed their effusions in the absence of chemotherapy.⁵ Risk factors for progression to active TB include recently acquired disease, immunocompromised status, increased exposure inoculum, and certain age groups (≤5 years, ≥60 years, or postpubertal adolescence).³ The overall incidence of TB is decreasing in the United States, but the proportion of cases among foreign-born children continues to rise. Haitian immigrants have rates of TB greater than 50 per 100 000 person years (>6 times the rate for the US population) in the first 5 years after arrival.⁶ Annually, about 1000 cases of pleural TB are reported in the United States. Although only 15% of patients with TB have extrapulmonary disease, roughly 1 in 30 have tuberculous pleural effusion.⁷

Accepted for publication April 18, 2000.

We thank Steven Moulton, MD, and Dongfen Chen, MD, for providing the photographs for the case, and to Jerome Klein, MD, for his editorial assistance.

Reprints: Katherine Hsu, MD, Boston University Medical Center, Section of Pediatric Infectious Diseases, Finland Labs 502, 774 Albany St, Boston, MA 02118-2393 (e-mail: khsu@bu.edu).