Langerhans Cell Histiocytosis: A case of predominant pulmonary presentation of multisystem disorder in an adolescent

A 15-year-old boy presented with recent onset of breathlessness, weight loss, and tiredness for two months and a crusting erythematous scalp rash for six months. The investigations revealed neutrophilia, raised C-reactive protein (CRP), and Alanine Aminotransferase (ALT). The blood urea and electrolytes, thyroid function tests, anti-nuclear antibodies, and clotting studies were normal

The chest radiograph (CXR) showed extensive bilateral, predominantly mid and upper zone, consolidation containing several foci of cavitation (Fig 1). There were also some ring shadows (Fig 1). Hilar and mediastinal contours were normal and there was no pleural effusion or pneumothorax. Bones appeared normal.

An inspiratory volumetric High-Resolution Computed Tomography (HRCT) demonstrated multiple bilateral cystic areas of varying morphology affecting most lung zones, including the costophrenic angles with a predominance of the upper zones (Fig 2a and 2b). There were also a few nodules in both the upper lobes and the middle lobe, some of which showed cavitation (Fig 2a and 2b). There was no lymphadenopathy. A solitary 12 mm lytic focus was noted within the sternum (Fig 3). These imaging findings were consistent with Langerhans Cell Histiocytosis (LCH) and the patient went on to have other investigations including a skeletal survey, bone scan, and ultrasound abdomen, none of which revealed other sites of disease. The diagnosis was confirmed by lung biopsy.

Langerhans cell histiocytosis (LCH) is a type of histiocytic disorder characterized by the infiltration of tissues by Langerhans cells [1].  Infiltrations are seen in bone (80%), skin (33%), pituitary (25%), liver, spleen, hematopoietic system and lungs (15% each), lymph nodes (5-10%), and the central nervous system (2-4%) [2]. Isolated pulmonary LCH (PLCH) is more frequent in adults and has a strong association with smoking [3] whereas, in children, it is seen as part of multisystem involvement [4].

PLCH is thought to be due to the uncontrolled proliferation of Langerhans cells mainly in the bronchial and bronchiolar epithelium [4]. This leads to the formation of granulomas, cavitation, and cyst-like lesions [4]. 

The commonest chest symptoms of PLCH are dry cough, breathlessness, and pleuritic chest pain. Systemic symptoms include fatigue, weight loss, fever, nausea, vomiting, malaise, anorexia, and night sweats whilst 25% of patients may be asymptomatic [3]. Spontaneous pneumothorax from rupture of subpleural cysts occurs in 10–20% of children [4].  

The CXR findings vary with the stage of the disease [4]. Reticulonodular changes in the early stages evolve into cystic changes in the advanced stage (see Fig 1) [5]. The distribution is typically diffuse, bilateral, and symmetrical [3, 4]. In end-stage PLCH, coarse reticular areas of opacity seen in the upper and middle lung zones may progress to honeycomb lung [3].

HRCT is better than CXR in characterising lung abnormalities [3]. In the early stage, nodular or reticulonodular interstitial opacities (0.5mm to 10mm) are seen in centrilobular, peribronchial, or peribronchiolar locations with surrounding normal lung parenchyma [3,4].

In advanced disease, thin-walled cystic lesions (<10 mm) predominantly involve the upper zones (see Fig 2a and 2b) [4]. Subtle cystic lesions are best demonstrated on Minimum IP images [4].

In the end stage, lung fibrosis develops with coarse reticular opacities and honeycombing typically affecting the upper and middle zones [3]. The lung volumes are usually preserved or even increased [3].

The clinical and characteristic imaging findings have a diagnostic accuracy of 72% [4]. Unlike in adults, the costophrenic angles are often involved in children (see Fig 2b) [4, 6]. Lung biopsy is required for definitive diagnosis, especially in cases with atypical features [5].

Multi-system LCH or rapidly progressive PLCH is treated with chemotherapy [3, 4]. Patients unresponsive to chemotherapy could be considered for lung transplant [3, 4]. The prognosis of PLCH in children is unclear, being rare [4].

Teaching points

1. Pulmonary LCH is often seen as part of multisystem involvement in children.
2. Imaging, particularly HRCT, plays an important role in diagnosis.

Written informed patient consent for publication has been obtained.

Differential diagnosis list

- Langerhans Cell Histiocytosis

- Tuberculosis (TB) – Primary TB disease risk is greatest in infants whereas, post-primary pulmonary TB is more commonly seen in adults with a peak between 20-30 years [7].

- Sarcoidosis – usually presents between 20-40yrs of age

- Granulomatosis with polyangiitis – typically occurs between 45-60yrs of age but may affect children and adolescents in up to 7% of cases [8]

- Lymphangioleiomyomatosis – commonly affects women of reproductive age.