Journal Mobile Options
Table of Contents
Vol. 69, No. 5, 2002
Issue release date: September–October 2002
Respiration 2002;69:468–470
(DOI:10.1159/000064013)

Necrotizing Sarcoid Granulomatosis Presenting with Elevated Serum Soluble Interleukin-2 Receptor Levels

Harada 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
email Corresponding Author

Abstract

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.


 Outline


 goto top of outline Key Words

  • Necrotizing sarcoid granulomatosis
  • Soluble interleukin-2 receptor
  • Sarcoidosis

 goto top of outline Abstract

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.

Copyright © 2002 S. Karger AG, Basel


goto top of outline Introduction

In 1973, Liebow [1] 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.

 

goto top of outline Case Report

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.

FIG01

Fig. 1. The CT scan shows multiple pulmonary nodules with cavitation.

FIG02

Fig. 2. Microscopically, necrotizing granuloma and angiocentric granulomatous vasculitis (arrow) are seen. HE. Original magnification ×36.

 

goto top of outline Discussion

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 [2]. 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 [3]. 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 [4].

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 [6]. 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.


 goto top of outline References
  1. Liebow AA: Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973;108:1–18.
  2. Tsukamoto K, Honda A, Kotani I, Eto T, Ota S, Suzuki H, Sato A: A case of necrotizing sarcoid granulomatosis [Japanese with English abstract]. Nihon Kyobu Shikkan Gakkai Zasshi 1995;33:181–186.
  3. Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL: Soluble interleukin-2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985;135:3172–3177.
  4. Nakashima H, Sugimoto M, Ikeda K, Ando M, Araki S: Serum levels of soluble IL-2 receptor and clinical course in patients with sarcoidosis [Japanese with English abstract]. Kokyu 1990;9:225–228.
  5. Churg A, Carrington CB, Gupta R: Necrotizing sarcoid granulomatosis. Chest 1979;76:406–413.
  6. Niimi H, Hartman TE, Müller NL: Necrotizing sarcoid granulomatosis: Computed tomography and pathologic findings. J Comput Assist Tomogr 1995;19:920–923.
  7. Adams DO: The granulomatous inflammatory response. A review. Am J Pathol 1976;84:164–191.

 goto top of outline Author Contacts

Toshiyuki Harada
First Department of Medicine, Hokkaido University School of Medicine
North 15, West 7, Kita-ku, Sapporo, 060-8638 (Japan)
Tel. +81 11 7161161, ext. 5911, Fax +81 11 7067899, E-Mail t-harada@med.hokudai.ac.jp


 goto top of outline Article Information

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


 goto top of outline Publication Details

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)

Journal Editor: C.T. Bolliger, Cape Town
ISSN: 0025–7931 (print), 1423–0356 (Online)

For additional information: http://www.karger.com/journals/res


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

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.



 goto top of outline Author Contacts

Toshiyuki Harada
First Department of Medicine, Hokkaido University School of Medicine
North 15, West 7, Kita-ku, Sapporo, 060-8638 (Japan)
Tel. +81 11 7161161, ext. 5911, Fax +81 11 7067899, E-Mail t-harada@med.hokudai.ac.jp


 goto top of outline Article Information

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


 goto top of outline Publication Details

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)

Journal Editor: C.T. Bolliger, Cape Town
ISSN: 0025–7931 (print), 1423–0356 (Online)

For additional information: http://www.karger.com/journals/res


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Liebow AA: Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973;108:1–18.
  2. Tsukamoto K, Honda A, Kotani I, Eto T, Ota S, Suzuki H, Sato A: A case of necrotizing sarcoid granulomatosis [Japanese with English abstract]. Nihon Kyobu Shikkan Gakkai Zasshi 1995;33:181–186.
  3. Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL: Soluble interleukin-2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985;135:3172–3177.
  4. Nakashima H, Sugimoto M, Ikeda K, Ando M, Araki S: Serum levels of soluble IL-2 receptor and clinical course in patients with sarcoidosis [Japanese with English abstract]. Kokyu 1990;9:225–228.
  5. Churg A, Carrington CB, Gupta R: Necrotizing sarcoid granulomatosis. Chest 1979;76:406–413.
  6. Niimi H, Hartman TE, Müller NL: Necrotizing sarcoid granulomatosis: Computed tomography and pathologic findings. J Comput Assist Tomogr 1995;19:920–923.
  7. Adams DO: The granulomatous inflammatory response. A review. Am J Pathol 1976;84:164–191.