Abnormal Fluorodeoxyglucose PET in Pulmonary Langerhans Cell Histiocytosis

doi:10.1378/chest.08-1899

Chest

Volume 135, Issue 6, June 2009, Pages 1542-1549

https://doi.org/10.1378/chest.08-1899 Get rights and content

Background

Pulmonary Langerhans cell histiocytosis is an inflammatory lung disease strongly associated with cigarette smoking and an increased risk of malignant neoplasms. Although the chest CT scan characteristics of PLCH are well recognized, the PET scan characteristics of adults with PLCH are unknown.

Methods

We identified 11 patients with PLCH who underwent PET scanning over a 6-year period from July 2001 to June 2007. The presenting clinicoradiologic features including PET scan and chest CT scan findings were analyzed.

Results

Five of 11 patients had positive PET scan findings. Of the five PET scan-positive patients, 4 were women, 4 (80%) were current smokers, and the median age was 45 years (age range, 31 to 52 years). PET scan-positive findings were more likely to be present if the scan was performed early in the clinical course. Three PET scan-positive patients (60%) had multiorgan involvement. PET scan-positive patients had predominantly nodular inflammatory lung disease (> 100 nodules) with most nodules measuring < 8 mm, whereas all PET scan-negative patients had predominantly cystic lung disease with fewer nodules (< 25 nodules). Notable abnormal PET scan findings included foci of increased uptake in nodular lung lesions, thick-walled cysts, bone, and liver lesions. The mean maximum standardized uptake value of the PET scan-positive lesions ranged from 2.0 to 18.2.

Conclusions

PLCH may be associated with abnormal thoracic and extrathoracic PET scan results. Patients with nodular disease seen on chest CT scans appear more likely to have abnormal PET scan findings. Our results suggest that PET scan imaging cannot reliably distinguish between the benign inflammatory nodular lesions of PLCH and malignant lesions.

Section snippets

Patient Selection

A computer-aided search was conducted to identify all adults (≥18 years of age) who were seen at the Mayo Clinic (Rochester, MN) during a 6-year period from July 1, 2001, to June 30, 2007, who had received a diagnosis of PLCH. We identified 207 patients, of whom 11 had undergone PET scanning. Indications for the PET scans included workup of indeterminate pulmonary nodules (two patients), concern for malignancy in patients with known PLCH (two patients), and evaluation of possible multiorgan

Demographic and Clinical Features

Eleven patients with PLCH underwent a PET scan during the study period; pertinent demographic and clinical data are included in Table 1. The mean age of the PLCH patient cohort was 36 years of age (age range, 26 to 52 years); nine patients (82%) were women. All 11 patients had a history of smoking, with 6 patients being current smokers at the time of evaluation. Nine patients presented with respiratory symptoms, most commonly dyspnea (64%), followed by cough (55%) and chest pain (36%).

Five of

Discussion

Our study indicates that FDG-PET scan results can be abnormal in adults with PLCH. Although FDG-PET scanning is currently not routinely performed in the evaluation of patients with PLCH, it may be obtained in certain clinical contexts. Although the presence of characteristic chest radiologic findings (nodules and cysts predominantly in the upper lung zones with relative sparing of the lung bases15, 16) may suggest the diagnosis of PLCH in some patients, various atypical findings have also been

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International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults
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Citation Excerpt :
Clinicians should be aware of the occurrence of second malignancies at any time point (before, during, or after) in relation to the LCH diagnosis as this may influence surveillance and management. LCH has diverse manifestations in adults, with varying frequencies of disease sites based mostly upon institutional retrospective series (Figure 1; Table 3; supplemental Appendix 2).6,15,33,37-81 Clinicians should be familiar with the clinical and radiographic features of LCH and attempt to pursue comprehensive evaluation at baseline given the implications for diagnosis and management of the disease.
Langerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of ¹⁸F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.
Smoking-Related—Interstitial Lung Disease
2021, Encyclopedia of Respiratory Medicine, Second Edition
This article highlights the smoking-related interstitial lung diseases including respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans cell histiocytosis (PLCH), combined pulmonary fibrosis and emphysema (CPFE) and smoking-related interstitial fibrosis (SRIF). All share cigarette smoking as a likely cause of presenting disease, of which characteristic clinical findings, radiologic features, and histopathology will be reviewed. For a majority of the smoking-related interstitial lung diseases, smoking cessation is a vital first step to reversing disease course or slowing progression, along with directed anti-inflammatory or immunosuppressant therapy.
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Le lien entre le tabagisme et l’HL pulmonaire de l’adulte est très étroit.
Le diagnostic de certitude est histologique. Dans un certain nombre de cas, il peut être retenu sur des critères radio-cliniques devant un aspect nodulo-kystique typique à la tomodensitométrie de haute résolution (TDM-HR) et un tableau clinique compatible.
Les principaux diagnostics différentiels à envisager varient selon l’aspect nodulo-kystique ou kystique isolé et le contexte clinique.
L’histoire naturelle de la maladie est mieux connue et l’évaluation régulière de la fonction respiratoire est essentielle pour le suivi des patients.
La maladie peut régresser ou demeurer stable et peu sévère sans traitement dans un nombre significatif de cas. Le sevrage tabagique est la première mesure essentielle car il diminue le risque de progression précoce de la maladie.
La cladribine est le seul traitement qui a montré une amélioration de la fonction respiratoire. Son efficacité et sa tolérance seront précisées prochainement.
Les thérapies ciblées des mutations de la voie des MAPK constituent une nouvelle arme thérapeutique qui reste à évaluer de façon rigoureuse dans l’atteinte pulmonaire de l’HL.
There is a strong relationship between tobacco smoking and pulmonary Langerhans cell histiocytosis (LCH) in adults.
Definitive diagnosis relies on lung histology. In certain cases, the diagnosis can be retained on a typical nodulo-cystic pattern on lung high-resolution computed tomography (HRCT) and appropriate clinical setting.
The main differential diagnoses to consider vary according to nodulo-cystic or only cystic pattern on lung HRCT and the clinical context.
The natural history of the disease is better known and regular evaluation of respiratory function is essential during the follow-up of the patients.
The disease may regress or remain stable and mild without treatment in a significant number of cases. Smoking cessation is the essential first step because it reduces the risk of early disease progression.
Cladribine is the only treatment that has shown improvement in respiratory function. Its efficacy and tolerance will be clarified in the near future.
Therapies targeting mutations in the MAPK pathway represent new therapeutic options that need to be appropriately evaluated pulmonary LCH.
Langerhans Cell Histiocytosis and Other Histiocytic Diseases of the Lung
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Citation Excerpt :
In the setting of constitutional symptoms or bone pain suggestive of systemic disease, PET may be useful. A PET scan can identify sites of multisystem LCH involvement, can elucidate concurrent disease processes (such as lymphoma), and has been described as a biomarker to assess response to therapy.39 One-fifth of PLCH patients have normal spirometry, diffusing capacity, and lung volumes at the time of diagnosis.4
Pulmonary manifestations of Langerhans cell histiocytosis
2015, Revue des Maladies Respiratoires
L’histiocytose langerhansienne pulmonaire est une pneumopathie infiltrante diffuse kystique rare, de cause inconnue, qui touche électivement les jeunes patients fumeurs des deux sexes. Les travaux multicentriques menés par le centre de référence ont permis de mieux connaître l’histoire naturelle à court et moyen termes de la maladie et de préciser les modalités de suivi des patients. Une altération importante de la fonction respiratoire peut survenir précocement après le diagnostic chez une proportion significative de patients. Le risque d’une telle évolution diminue après le sevrage tabagique. La cladribine, cystostatique analogue des purines, peut entraîner une amélioration franche de la fonction respiratoire des patients ayant une forme clinique progressive de la maladie, mais ce traitement demeure du domaine de la recherche clinique. Les traitements spécifiques de l’hypertension pulmonaire (anti-récepteurs de l’endothéline, inhibiteurs des phosphodiestérases) peuvent être utilisés avec prudence chez les patients ayant une hypertension pulmonaire sévère, dans des centres spécialisés. La mise en évidence de la présence de la mutation V600E de l’oncogène BRAF dans près de 50 % des lésions d’histiocytose langerhansienne, y compris pulmonaires, constitue une avancée importante dans la compréhension de la pathogénie de cette maladie et ouvre la voie à des approches thérapeutiques plus ciblées.
Pulmonary Langerhans cell histiocytosis is a rare diffuse cystic interstitial pneumonia of unknown etiology that occurs selectively in young smokers of both genders. The multicenter studies conducted by the reference center have better defined the short and medium terms natural history of the disease and the clinical management of patients. A substantial proportion of patients experience a dramatic decline in their lung function soon after diagnosis. Importantly, smoking cessation is associated with a decreased risk of subsequent deterioration. Cladribine, a purine analogue, chemotherapy may dramatically improve lung function in patients with progressive pulmonary Langerhans cell histiocytosis, but this treatment should be used only in the setting of clinical research. Specific pulmonary hypertension therapies (anti-endothelin receptors, inhibitors of phosphodiesterases) may be used with caution in specialized centres for patients with severe pulmonary hypertension, and seem to be well tolerated. The recent identification of the V600E mutation of the BRAF oncogene in approximately half of the Langerhans cell histiocytosis lesions, including pulmonary granulomas, represents an important step forward in the understanding of the pathogenesis of Langerhans cell histiocytosis. Potentially it opens the way to targeted therapies.
A 22-year-old nonsmoker with diffuse cystic lung disease
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The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

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Chest

Original ResearchInterstitial Lung DiseaseAbnormal Fluorodeoxyglucose PET in Pulmonary Langerhans Cell Histiocytosis

Background

Methods

Results

Conclusions

Section snippets

Patient Selection

Demographic and Clinical Features

Discussion

Clinical molecular imaging with positron emission tomography

Eur J Cancer

PET evaluation of lung cancer

J Nucl Med

Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis

JAMA

T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET

Radiology

PET/CT imaging techniques, considerations, and artifacts

J Thorac Imaging

Positron emission tomography/computed tomography: protocol issues and options

Semin Nucl Med

Pulmonary Langerhans'-cell histiocytosis

N Engl J Med

Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome

Cancer

Positron emission tomography imaging in nonmalignant thoracic disorders

Semin Nucl Med

Results of 188 whole-body fluorodeoxyglucose positron emission tomography scans in 137 patients with sarcoidosis

Chest

Idiopathic pulmonary fibrosis on F-18 FDG positron emission tomography

Clin Nucl Med

Idiopathic pulmonary fibrosis: evaluation with positron emission tomography

Respiration

Fluorine-18-fluorodeoxyglucose uptake in rheumatoid arthritis-associated lung disease in a patient with thyroid cancer

J Nucl Med

Coincidence FDG-PET in the evaluation of Langerhans' cell histiocytosis: preliminary findings

Pediatr Radiol

Pulmonary histiocytosis X: evaluation with high-resolution CT

Radiology

Accuracy of high-resolution CT in diagnosing lung diseases

AJR Am J Roentgenol

Original Research
Interstitial Lung Disease
Abnormal Fluorodeoxyglucose PET in Pulmonary Langerhans Cell Histiocytosis