Lack of Evidence for an Association Between Neurofibromatosis and Pulmonary Fibrosis

doi:10.1378/chest.128.4.2381

Chest

Volume 128, Issue 4, October 2005, Pages 2381-2386

https://doi.org/10.1378/chest.128.4.2381 Get rights and content

Study objectives

To reassess the association between neurofibromatosis and pulmonary fibrosis.

Design

Retrospective single-center study with analysis of patients' chest radiographs, CT scans, and medical records.

Setting

Tertiary care, referral medical center.

Patients

One hundred fifty-six adult patients with neurofibromatosis seen over a 6-year period between 1997 and 2002.

Results

A review of chest radiographs revealed abnormal findings in 70 patients (44.9%). The most common radiographic abnormalities were extrapulmonary nodules or masses seen in 22 patients (14.1%), followed by skeletal abnormalities in 16 patients (10.3%). Bilateral interstitial infiltrates were noted in only three patients (1.9%), all of whom had potential causes other than neurofibromatosis for their lung infiltrates, including smoking-related interstitial lung disease, rheumatoid lung disease, recurrent pneumonias, and a history of ARDS. CT scans were available in two of these patients and revealed nonspecific patterns of abnormalities with no honeycombing. Six patients had bullae or cystic airspaces demonstrated on chest radiography or CT scan; all of these findings occurred in the context of smoking-related emphysema. Combined together, bilateral interstitial lung infiltrates or cystic airspaces were demonstrated in five patients (3.2%) by chest radiography, and in eight patients (5.1%) by chest radiography or CT scanning; one patient had both findings on the CT scan.

Conclusions

We found little evidence to support an association between neurofibromatosis and pulmonary fibrosis or any other form of parenchymal lung disease. Interstitial lung disease and bullae described in association with neurofibromatosis in previous reports may have, in part, represented smoking-induced manifestations.

Section snippets

Materials and Methods

We conducted a computer-assisted search of the Mayo Clinic database to identify patients with NF who were seen at our institution over a 6-year period between January 1, 1997, and December 31, 2002. This search was limited to adults (≥ 21 years of age) since pulmonary fibrosis associated with NF has previously been reported only in adults with this disorder.

We identified 163 adults with NF who underwent chest radiography during their clinical evaluation at our medical center. Of these 163

Results

Demographic and clinical characteristics of the 156 patients included in this study are outlined in Table 1. The median age of these adults with NF was 43 years, and approximately two thirds of them were nonsmokers. The number of patients with NF1 exceeded that of patients with NF2 by a ratio of 5.5:1. The primary indications for referral (or self-referral) of these patients to our institution included neurologic manifestations in 56 patients (35.9%), dermatologic manifestations in 15 patients

Discussion

Although previous studies had described up to a 23% prevalence of parenchymal lung disease detected among patients with NF,⁶ we found little evidence to support a true association between NF and pulmonary fibrosis. We identified only three patients (1.9%) with bilateral interstitial infiltrates seen on chest radiography. All three patients had potential causes other than NF for their interstitial lung infiltrates, including smoking-related interstitial lung disease, rheumatoid lung disease,

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When discussing cystic lung diseases, a certain group of diseases tends to receive the majority of attention. Other less frequently discussed cystic lung diseases are also important causes of morbidity in patients. Etiologies include genetic syndromes, lymphoproliferative diseases, infections, exogenous exposures, and a developmental abnormality. This review article focuses on the clinical and imaging features of these other cystic lung diseases.
A Case of Non–Small-cell Lung Cancer in a Patient With Neurofibromatosis Type 1
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Neurofibromatosis type 1 is an autosomal dominant condition that classically presents with café au lait spots, cutaneous neurofibromas, axillary and inguinal freckling, and iris Lisch nodules. Patients diagnosed with NF-1 have an increased risk of malignancy, due to mutations associated with the tumour suppressor gene p53, however pulmonary malignancies are relatively uncommon. A 39-year-old female patient previously diagnosed with NF-1 presented with progressive dyspnoea and chest pain. Chest radiography and computed tomography (CT) demonstrated a left apical lung mass with mediastinal and pericardial infiltration. Metastatic deposits were identified in the brain, adrenal glands and thoracic spine on CT brain, chest and abdomen. Echocardiogram demonstrated a left ventricular mass suggestive of a cardiac fibroma with evidence of inferior vena cava invasion. Biopsy of a supraclavicular lymph node was performed and revealed a diagnosis of non-small cell lung adenocarcinoma. Lung cancer is an uncommon malignancy in the NF-1 population. This case report details a rare case of non-small cell lung cancer in a patient with NF-1, and highlights the need to consider the diagnosis of lung cancer in patients with NF-1 presenting with symptoms suggestive of pulmonary malignancy.
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Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is an autosomal dominant dysplasia of the ectoderm and mesoderm with a variable clinical expression, but near-complete penetrance before the age of 5 years. The estimated incidence is 1 in 3000 births. NF-1 is characterized by collections of neurofibromas, café-au-lait spots, axillary and inguinal freckling, and pigmented hamartomas in the iris (Lisch nodules). Pulmonary manifestations of NF-1, which usually include bilateral basal reticulations and apical bullae and cysts, are reported in 10–20% of adult patients. Clinically, neurofibromatosis-associated diffuse lung disease (NF-DLD) usually presents with nonspecific respiratory symptoms, including dyspnea on exertion, shortness of breath, and chronic cough or chest pain, at the time of diagnosis. Computed tomography (CT) is highly accurate for the identification and characterization of NF-DLD; it is the most reliable method for the diagnosis of this lung involvement. Various CT findings of NF-DLD, including cysts, bullae, ground-glass opacities, bibasilar reticular opacities, and emphysema, have been described in patients with NF-1. The typical CT pattern, however, is characterized by upper-lobe cystic and bullous disease, and basilar interstitial lung disease. Currently, the goal of NF-DLD treatment is the earliest possible diagnosis, focusing on symptom relief and interventions that positively alter the course of the disease, such as smoking cessation. The aim of this review is to describe the main clinical, pathological, and imaging aspects of NF-1, with a focus on pulmonary involvement.
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Although previously reported, the existence of a neurofibromatosis (NF)-associated diffuse lung disease (DLD) still lacks solid evidence. We report a case of a 68-year-old non-smoking female with NF1, pre-capillary pulmonary hypertension (PH) and an interstitial lung pattern. Initial findings included progressive dyspnea, hypoxemia and sparse centrilobular ground-glass micronodules on high-resolution computed tomography (HRCT). Further study demonstrated a severe defect in diffusing capacity for carbon monoxide (DLCO), macrophages on bronchoalveolar lavage and pre-capillary PH on right cardiac catheterization. Surgical biopsy revealed macrophage accumulation along bronchovascular bundles and alveolar spaces and type II pneumocytes hyperplasia. Given the absence of environmental exposure or new drugs, a NF-DLD was hypothesized. Pre-capillary PH was disproportionate to interstitial findings, so it was attributed to a NF1-vasculopathy. Treatment with triple sequential combined therapy was unsuccessful culminating in death 18 months later. This case adds HRCT and anatomopathological data suggesting NF-DLD as a distinct manifestation of the disease.

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This research was supported by the Robert N. Brewer Family Foundation

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

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Chest

Clinical InvestigationsLack of Evidence for an Association Between Neurofibromatosis and Pulmonary Fibrosis

Study objectives

Design

Setting

Patients

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Neurol Clin

Mayo Clin Proc

Radiol Clin North Am

Am J Med

Chest

Respir Med

Mayo Clin Proc

Chest

Recent advances in neurofibromatosis type 1

Curr Opin Neurol

Neurofibromatosis 2

Curr Opin Neurol

Fibrosing alveolitis: its occurrence, roentgenographic and pathologic features in von Recklinghausen's neurofibromatosis

Am Rev Respir Dis

Neurofibromatosis (von Recklinghausen's disease): an unusual cause of parenchymal lung disease

S Afr Med J

Interstitial lung disease in neurofibromatosis

South Med J

Clinical Investigations
Lack of Evidence for an Association Between Neurofibromatosis and Pulmonary Fibrosis