Cystic lung disease

When our colleagues from Radiology are confronted with cystic changes on high-resolution CT scans, their differential diagnoses include emphysema; cystic bronchiectasis; honeycomb change; cavitated infective nodules (including mycobacterial infection and septic embolism); other cavitated nodules such as Wegener's granulomatosis and necrotising sarcoid granulomatosis; Langerhans cell histiocytosis (LCH); lymphangioleiomyomatosis; lymphocytic interstitial pneumonia; follicular bronchiolitis; amyloidosis; light chain deposition disease (LCDD); Birt-Hogg-Dubé syndrome (BHDS); and cystic metastases. 1

Most of these entities can be readily distinguished in the light of the clinical features and are not often biopsied. The entities to be addressed here are those most likely to be encountered by pathologists when confronted with a clinical scenario of diffuse cystic lung disease, excluding congenital and paediatric cystic diseases.

Langerhans cell histiocytosis

Langerhans cells are differentiated cells of monocyte-macrophage lineage, which represent an immature stage in the development of dendritic cells. They are actively motile and function as antigen-presenting cells. They are found principally in stratified squamous epithelia, but are also present in lymph nodes, thymic epithelium and bronchial mucosa. They express major histocompatibility complex class II molecules, CD1a and S100 protein but not CD68. They are derived from a primitive CD34 monocyte precursor in bone marrow and can be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-α. 2-4

At light microscopy, Langerhans cells are 12-15 microns in diameter and have moderate amounts of eosinophilic cytoplasm that contains few, if any, phagocytised particles. Their nuclei are vesicular with finely granular chromatin, inconspicuous nucleoli, and a characteristic grooved or convoluted appearance. 2-4 At electron microscopy, pentilaminar Birbeck (Langerhans) granules (bodies) are pathognomonic. 2

The terminology surrounding lesions derived from Langerhans cells is confusing. Histiocytosis X was the term applied by Lichtenstein in 1953 to a group of conditions previously designated as eosinophilic granuloma of bone, Letterer-Siwe disease and Hand-Schuller-Christian disease. Letterer-Siwe disease (acute disseminated LCH) is a potentially fatal systemic disease of children under three. Hand-Schuller-Christian disease is a multifocal disease of early childhood commonly affecting lungs and bones and classically presenting with the triad of bone defects, exophthalmos and diabetes insipidus. Single system disease (eosinophilic granuloma and Pulmonary Langerhans cell histiocytosis (PLCH) involves a single organ (bone, lungs or skin), usually follows a benign course and can regress spontaneously. Since proliferation of the Langerhans cell...