Table  2

Characteristics of different diffuse cystic lung diseases

LAMPLCHBHDLymphocytic interstitial pneumoniaAmyloidosisLight chain deposition diseaseInfection
  • Proliferation of abnormal smooth-like muscle cells (LAM cells)

    Sporadic or autosomal dominant (TSC-LAM)

  • Infiltration and destruction by CD1a+ Langerhans-like cells

  • Autosomal dominant (FLCN gene)

  • Diffuse reactive pulmonary lymphoid hyperplasia

    Idiopathic or associated with an underlying immunological condition

  • Misfolding protein and its extracellular deposition as fibrils

  • Accumulation of monoclonal light chain secreted by a clone of plasma cells

  • PJP: fungal infection

    RRP: HPV-6 and -11

Clinical Hx
  • Occurs almost exclusively in women

  • Young smokers

    Both sexes

  • Relative with BHD or FHx of pneumothoraces, skin lesions and renal cancer

  • Hx of autoimmune conditions or immunological conditions, e.g. Sjögren syndrome, HIV

  • Presents in the sixth decade of life

    Hx of Sjögren syndrome, lymphoproliferative disease or lymphoma

  • Lymphoproliferative disorders

  • PJP: immunocompromised host

    RRP: upper airway symptoms (hoarse voice, wheeze, stridor)

Distribution of cysts
  • Diffuse

    No lobar predominance

  • Upper and middle lobes

    Sparing costophrenic angles

  • Basal predominance



  • Diffuse (often subpleural and perivascular)

  • Diffuse

  • Diffuse

  • PJP: upper lobe predominance

    RRP: predominately lower lobes

  • Round

  • Irregular

  • Round, elliptiform, lentiform

  • Round

  • Round

  • Round

  • Variable

Other findings on HRCT
  • Chylous pleural effusions

  • Symmetric reticulo-micronodular infiltration ±cavities

  • Nil

  • Ground-glass infiltrates, poorly defined centrilobular nodules, interlobular septal thickening

  • Multiple nodules abutting cyst walls

  • Multiple nodules

  • PJP: bilateral ground glass (apical predominance, peripheral sparing), consolidation, linear reticular opacities, nodules, parenchymal cavities

    RRP: solid nodules, tracheal wall irregularities, bronchiectasis

Extrapulmonary manifestations
  • Renal angiomyolipomas

    Chylous effusions (pleural or ascites)


    TSC: skin lesions, seizures, hamartomatous lesions in various organs

  • Adult PLCH is generally isolated

    Rarely: bones (lytic lesions), pituitary (diabetes insipidus), skin rash

  • Skin fibrofolliculomas

    Renal tumours

  • Autoimmune diseases and associated symptoms including sicca symptoms and Raynaud's

  • Renal, cardiac, gastrointestinal, neurological and skin manifestations

  • Renal failure

    Lymphoproliferative disorders

  • PJP: immunosuppression, constitutional features

    RRP: upper airway involvement

Supporting investigations
  • VEGF-D >800 pg·mL−1

    Tbbx or VATS biopsy

  • BRAF mutation testing

    Tbbx or VATS biopsy

  • Genetic testing for FLCN mutations

    Imaging for renal tumours

    Skin biopsy

  • Autoimmune panel

    HIV testing

    VATS biopsy

  • Presence of monoclonal protein

    VATS biopsy

  • Investigation for lymphoproliferative disorder

    Renal biopsy

    VATS biopsy

  • HIV status, CD4+ cell count

    PCR of induced sputum, BAL fluid or nasopharyngeal aspirates

  • mTOR inhibition: everolimus, sirolimus

  • Smoking cessation

  • Nil

  • Corticosteroids and immunosuppression

  • Treatment of underlying disease

  • Treatment of underlying disease

  • PJP: trimethoprim-sulfamethoxazole

    RRP: cidofovir

PLCH: pulmonary Langerhans cell histiocytosis; BHD: Birt–Hogg–Dubé syndrome; Hx: history; FLCN: folliculin; PJP: Pneumocystis jirovecii pneumonia; RRP: recurrent respiratory papillomatosis; HPV: human papilloma virus; FHx: family history; VEGF: vascular endothelial growth factor; Tbbx: transbronchial biopsy; VATS: video-assisted thoracoscopic surgery; BAL: bronchoalveolar lavage; mTOR: mammalian target of rapamycin.