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Isolated pulmonary langerhans-cell histiocytosis mimicking miliary tuberculosis/Miliyer tuberkulozu taklit eden izole pulmoner langerhans hucreli istiositoz olgusu.


Pulmonary Langerhans'-cell histiocytosis LCH) forms part of a spectrum of diseases characterized by monoclonal proliferation and infiltration of organs by Langerhans' cells (1). Isolated type pulmonary disease occurs predominantly in adults, whereas this is rare in children (2). The adult predominance reflects the only consistent epidemiologic association; cigarette smoking is present in an overwhelming majority (1).

Spontaneous pneumothorax (PTX) occurs in approximately 10% of children with pulmonary LCH, and may show recurrence in adulthood (3). Although recurrent PTXs have a poor long-term outcome in adults, its prognostic significance is unclear in the pediatric age group because of the limited case number. Regarding the literature, the majority of subjects may have a fatal outcome despite being diagnosed and treated properly.


Case Report

A seventeen-month old female patient was admitted to our tertiary-care teaching hospital with the complaints of worsening malaise, fever and cough for the previous 2 months. Despite the use of wide-spectrum antibiotics for 3 weeks, her clinical picture had not improved at a local hospital. Appearance of reticulo-nodular image on the most recent chest X-ray (CXR) caused her transfer to our clinic with the presumptive diagnosis of miliary tuberculosis.

There was a reported pulmonary tuberculosis case in an adult relative who had occasionally visited the family. Hepatomegaly was the only pathologic finding on physical examination. The respiration rate, type and auscultation findings were regular. Her growth parameters were also within the normal range.

The hemogram, liver function tests, sweat chloride test and immune status showed normal results. Her PPD test provoked no response, and close contact screening of the family for tuberculosis was negative. Abdominal ultrasonography revealed diffuse hepatomegaly. We continued the four-drugs antituberculosis therapy which was ordered at the previous healthcare centre.



Her follow-up CXRs showed not only a disseminating reticulo-nodular pattern but also a cystic appearance. High-resolution computed tomography (HRCT) of the thorax demonstrated peribronchial nodules and cystic changes which were less than 20 mm in diameter and typically had a thin wall (Fig. 1). Since the HRCT findings were not compatible for miliary tuberculosis, we performed open lung biopsy upon gradual development of cyanosis and dyspnea. Histology showed an infiltration composed of lymphocytes, plasma cells, eosinophils and histiocytes which had abundant cytoplasm, and large nuclei with a coffee bean configuration characteristic of Langerhans' cells (Fig. 2). Immunoperoxidase staining of the histiocytes revealed strong cytoplasmic positivity with S-100 protein antibody. In addition, immunohistochemistry showed dense infiltration of CD1a stained Langerhans' cells (Fig. 3). Concurrent radiological and scintigraphic evaluation of bones, bone marrow evaluation and cranial MRI showed no pathology.


She developed a right-sided PTX (Fig. 4) five days after operation which was successfully drained. However, the next 38 days saw an undulating clinical course due to recurrent bilateral PTXs (a total of four independent episodes). All the episodes were ameliorated by under-water sealed drainage and conservative interventions. Her initial chemotherapy for pulmonary LCH consisted of continuous methylprednisolone and mercaptopurine (6MP) tablets plus weekly etoposide and vinblastine injections. The patient responded well to this regimen, and was free of initial symptoms in her 12th month follow-up. However, mild to moderate pulmonary fibrosis developed which is an important mechanism of lung remodelling.


The miliary pattern is a well-known chest radiographic pattern, consistent with the multiple nodules in the lung. A heterogeneous group of conditions comprising more than 80 entities may display this pattern (4). Random nodules are uniform and even in distribution which is the probable form in disseminated granulamatous infections such as tuberculosis or fungal disease (5).

Miliary tuberculosis refers to hematagenous dissemination of tubercle bacilli in primary and post-primary tuberculosis. The CXR plays an important role in the diagnosis but is limited by its low sensitivity (6), 60%. HRCT allows early specific diagnosis by showing multiple, well-defined nodules appearing in a random pattern. In addition, associated features such as a preexisting tuberculosis lesion, consolidation with or without cavitations, small pleural effusions and mediastinal lymph nodes may be visible (5). Therefore, thoracic HRCT must be evaluated in the differential diagnosis of a miliary pattern before initiating antituberculosis therapy, even in high-prevalence countries.

The most common presenting symptoms of pulmonary LCH are nonproductive cough and dyspnea. Weight loss, night sweats and anorexia occur in up to a third of patients (7) mimicking M. tuberculosis infection. The most common early radiographi c abnormalities are bilateral, symmetric, peribronchiolar, micronodular and interstitial infiltration with a predominance of middle and upper lobe involvement (6) as in miliary tuberculosis. Cystic changes are commonly superimposed on a background of reticulonodular pattern as they become more prominent in the later stages of disease. Typically thin walled lung cysts are less than 20 mm in diameter and necessitate thoracic HRCT for a probable diagnosis (8). Disease progression is accompanied by the consecutive development of bullae and subsequent fibrosis yielding a "honey-combing" appearance.

Spontaneous PTXs are thought to arise from the rupture of a thin-walled subpleural cystic lesion (9), a complication seen infrequently in childhood . PTX can occur at any time throughout the disease, but are occasionally seen as the initial manifestation. PTX has been previously described as a postoperative complication, just as in this case (3). It is likely that mechanical ventilation during the operation induces the development. If at all possible, this procedure should be postponed in order to avoid recurrent PTXs which were reported to carry a poor prognosis in adults and children. Instead of invasive procedures, a combination of classical thoracic HRCT findings and immunocytochemical investigations of bronchoalveolar lavage (BAL), using anti-CD1a antibodies (10), should be preferred for the definite diagnosis of isolated pulmonary LCH and this in turn will also diminish complications.

No specific recommendations are present in the literature for the management of PTXs in the course of pediatric pulmonary LCH. This case underwent only under-water sealed drainage since the timing and importance of pleurodesis and thoracotomy for recurrent PTXs have not yet been established. The small number of pediatric cases presenting at individual centers, and conflicting results pertaining to each technique prevent the formation of consensus. We would like to emphasize that drainage and effective conservative follow-up may be enough for the management of PTXs in pediatric pulmonary LCH even in recurrent episodes, and sophisticated procedures should be reserved for unresponsive cases.

As a result, the miliary pattern necessitates thoracic HRCT for the differential diagnosis. The combination of thoraxcic HRCT and immunocytochemical investigations of BAL may be sufficient to diagnose pulmonary LCH. Mechanical ventilation must be undertaken with caution in pulmonary LCH, and if possible avoided. PTXs, even when recurrent, do not always imply a poor prognosis in the pediatric population.


(1.) Vassallo R, Ryu JH, Colby TV, Hartman T and Limper AH. Pulmonary Langerhans'-cell histiocytosis. New Engl J Med 2000; 342: 1969-78.

(2.) Nondahl SR, Findlay JL, Farrell PM, Warner TF, Hong R. A case report and literature review of primary pulmonary histiocytosis of childhood. Med Pediatr Oncol 1986; 14: 57-62.

(3.) Yule SM, Hamilton JRL and windebak KP. Recurrent pneumomediastinum and pneumothorax in Langerhans'-cell histiocytosis. Med Pediatr Oncol 1997; 29: 139-42.

(4.) Andreu J, Mauleon S, Pallisa E, Majo J, Martinez-Rodriguez M, Caceras J. Miliary lung disease revisited. Curr Probl Diagn Radiol 2002; 31: 189-97.

(5.) McGuinness G, Naidich DP, Jagirdar J, Leitman B, McCauley DI. High resolution CT findings in miliary lung disease. J Comput Assist Tomogr 1992; 16: 384-90.

(6.) Kwong JS, Carignan S, Kang E-Y, Muller NL, Fitzgerald JM. Miliary tuberculosis: Diagnostic accuracy of chest radiography. Chest 1996: 110: 339-42.

(7.) Travis WD, Borok Z, Roum JH, and et al. Pulmonary Langerhans cell granulomatosis: a clinicopathologic study of 48 cases. Am J Surf Pathol 1993; 17: 971-86.

(8.) Moore AD, Godwin JD, Muller NL,and et al. Pulmonary histiocytosis X: comparison of radiographic and CT findings. Radiology 1989; 172: 249-54.

(9.) Tazi A, Soler P, Hance AJ. Adult pulmonary Langerhans' cell histiocytosis. Thorax 2000; 55: 405-16.

(10.) Refabert L, Rambaud C, Mamou-Mani T, Scheinmann P, de Blic J. Cd1a-positive cells in bronchoalveolar lavage samples from children with Langerhans cell histiocytosis. J Pediatr 1996; 129: 913-5.

Metehan Ozen [1], Necla Akcakaya [2], Yildiz Camcioglu [2], Haluk Cokugras [2], Buge Oz [3]

[1] Inonu Universitesi Tip Fakultesi, Cocuk Enfeksiyon Hastaliklari Bilim Dali, Malatya, Turkiye

[2] Istanbul Universitesi Cerrahpasa Tip Fakultesi, Cocuk Enfeksiyon Hastaliklari Bilim Dali, Istanbul, Turkiye

[3] Istanbul Universitesi Cerrahpasa Tip Fakultesi, Patoloji Anabilim Dali, Istanbul, Turkiye

Gelis Tarihi: 22.11.2008

Kabul Tarihi: 17.01.2009

Correspondence Address:

Yazisma Adresi:

Dr. Metehan Ozen

Inonu Universitesi

Tip Fakultesi, Cocuk

Enfeksiyon Hastaliklari

Bilim Dali, Malatya, Turkiye

Phone: +90 532 283 07 21

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Article Details
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Author:Ozen, Metehan; Akcakaya, Necla; Camcioglu, Yildiz; Cokugras, Haluk; Oz, Buge
Publication:Journal of Pediatric Infection
Article Type:Case study
Geographic Code:7TURK
Date:Sep 1, 2009
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