Necrotizing Sarcoid Granulomatosis Presenting with Elevated Serum Soluble Interleukin-2 Receptor LevelsHarada T.a · Amano T.a · Takahashi A.a · Furuya J.a · Yamaguchi E.a · Kaji M.b · Morikawa T.b · Itoh T.c · Shimizu M.c · Nishimura M.a
aFirst Department of Medicine, bSecond Department of Surgery, Hokkaido University School of Medicine, and cDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan Corresponding Author
A 52-year-old woman presented with a one-week history of low-grade fever and dyspnea. A CT scan showed multiple pulmonary nodules with cavitation, as well as bilateral pleural thickenings with effusions. A specimen resected by video-assisted thoracoscopic surgery showed multiple confluent granulomas with central necrosis and granulomatous vasculitis. These findings were consistent with necrotizing sarcoid granulomatosis. An elevated serum soluble interleukin-2 receptor level became normal following clinical and radiological improvement. This indicates that the serum soluble interleukin-2 receptor can be a useful marker for the clinical management of necrotizing sarcoid granulomatosis.
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In 1973, Liebow  introduced the categories of pulmonary angiitis and granulomatosis, which included five different entities: Wegener’s granulomatosis, limited Wegener’s granulomatosis, lymphomatoid granulomatosis, bronchocentric granulomatosis, and necrotizing sarcoid granulomatosis (NSG). NSG has the following three characteristics: (1) histologically, there is a background of sarcoid-like granuloma, a prominent granulomatous vasculitis, and varying degrees of necrosis; the latter often superimposing upon a mass of confluent granulomas; (2) radiographically, there are usually pulmonary nodules but no enlarged hilar lymph nodes, and (3) clinically, the course is benign, even with minimal or no therapy. We here report a case of NSG presenting with an elevated serum soluble interleukin-2 receptor (sIL-2R) level.
A 52-year-old woman was admitted to our hospital because of low-grade fever and dyspnea of one week duration. She was a lifelong nonsmoker, and had no unusual travel history or occupational exposure. Upon physical examination she appeared obtunded, with an axillary temperature of 37.0°C. Her erythrocyte sedimentation rate (50 mm/h), C-reactive protein (2.16 mg/dl), and serum sIL-2R level (798 U/ml; normal: 121–383) were all elevated. The level of serum angiotensin-converting enzyme was normal. The levels of serum cytoplasmic and perinuclear antineutrophil cytoplasmic antibodies were normal. Tuberculin reaction was negative. A chest radiograph showed multiple pulmonary nodules with cavitation, predominantly in the bilateral upper zones of the lungs. This was confirmed by CT scans, which additionally showed bilateral pleural thickenings with small amounts of effusions; however, no hilar or mediastinal lymphadenopathy was noted (fig. 1). Bronchoalveolar lavage (BAL) was performed in the anterior segment of the right lung. In the BAL cell differential, there was a marked increase in lymphocytes (40.3%), and the CD4+/CD8+ ratio was as high as 4.68. Culture and cytology of BAL fluid, and brushing cytology from the apico-posterior segment of the left lung were negative. No extrapulmonary involvement was found. Suspecting NSG, we performed video-assisted thoracoscopic surgery and removed one nodule from the apico-posterior segment of the left lung. Histological examination revealed an active necrotizing granulomatous process along with granulomatous vasculitis (fig. 2). These granulomas were present along the lymphatic channels. Special stains and cultures for bacteria, fungi, and mycobacteria were negative. These findings are consistent with NSG. The patient was treated with 40 mg of predonisone per day. Her symptoms rapidly improved, and the lung lesions disappeared within two weeks, leaving some residual fibrosis. sIL-2R levels returned to normal range (187 U/ml) following clinical and radiological improvement. Six months later, she remained in a stable condition with 5 mg of predonisone per day.
Fig. 1. The CT scan shows multiple pulmonary nodules with cavitation.
Fig. 2. Microscopically, necrotizing granuloma and angiocentric granulomatous vasculitis (arrow) are seen. HE. Original magnification ×36.
More than 120 cases of NSG have been reported to date in the English language literature. Only one case of NSG with high lymphocytes and a sarcoidosis-like CD4+/CD8+ ratio in BAL fluid has been reported . However, there have been, to our knowledge, no reports on the level of sIL-2R in NSG cases. sIL-2R is expressed on the T cell surface and released in serum following T cell activation by the enhancement of immune response, such as in hematopoietic malignancies, autoimmune diseases, or chronic infectious diseases . The elevated sIL-2R level in this patient may reflect T cell activation in the lungs. sIL-2R could be a useful marker for evaluating the clinical course of NSG, as has been seen in some cases of sarcoidosis in which the elevated sIL-2R level returned to normal following radiological improvement .
The radiological pattern in the majority of patients with NSG is one of multiple well-defined nodules with a range in size from a few millimeters to 5 cm in diameter. Other radiological manifestations include a solitary nodule or mass, bilateral areas of consolidation, and, less commonly, a bilateral interstitial reticular pattern [5, 6]. On high-resolution CT, the nodules or the areas of consolidation have a predominantly peribronchial or subpleural distribution . Cavitation, pleural effusions, and hilar lymphadenopathy have been reported only infrequently (8, 11 and 28%, respectively). CT findings with cavitation of nodular infiltrate, pleural involvement, no hilar lymphadenopathy, and an absence of extrathoracic lesions are features that strongly suggest a diagnosis of NSG, such as seen in this case.
The morphologic and clinical diversity of NSG and the potential multiplicity of causes of granulomatous lung diseases have created considerable uncertainty as to the etiology and pathogenesis of NSG [1, 7]. NSG is an exclusion diagnosis and should not be diagnosed until all special stains and cultures have been performed to rule out any infectious causes, such as tuberculosis, atypical mycobacteriosis, and mycoses.
In summary, we here describe a case of NSG already suspected by CT findings and laboratory data. Our case is unique because NSG is usually recognized only after histologic examination of excised lung tissue. In addition, our case indicates that sIL-2R can be a useful marker for the clinical management of NSG.
First Department of Medicine, Hokkaido University School of Medicine
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Received: Received: August 7, 2001
Accepted after revision: February 4, 2002
Number of Print Pages : 3
Number of Figures : 2, Number of Tables : 0, Number of References : 7
Respiration (International Review of Thoracic Diseases)
Founded 1944 as ‘Schweizerische Zeitschrift für Tuberkulose und Pneumonologie’ by E. Bachmann, M. Gilbert, F. Häberlin, W. Löffler, P. Steiner and E. Uehlinger, continued 1962–1967 as ‘Medicina Thoracalis’ as of 1968 as ‘Respiration’, H. Herzog (1962–1997)
Official Journal of the European Association for Bronchology and Interventional Pulmonology
Vol. 69, No. 5, Year 2002 (Cover Date: September-October 2002)
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