Lung tumor
Benign tumors
Langerhans cell histiocytosis

Author: Roseann Wu, M.D. (see Authors page)

Revised: 23 March 2016, last major update March 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Langerhans cell histiocytosis [title] lung
Cite this page: Langerhans cell histiocytosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungtumorLCH.html. Accessed December 4th, 2016.
Definition / General
  • Proliferative disease or disorder of Langerhans cells involving lung, highly associated with smoking
  • Pulmonary Langerhans cell histiocytosis (PLCH) is thought to be distinct from systemic Langerhans cell histiocytosis (LCH)
  • Most common pulmonary histiocytic lesion (Arch Pathol Lab Med 2008;132:1171)
Essential Features
  • Almost exclusively seen in young to middle aged smokers
  • Stellate nodules centered around small airways, with early cellular phase and later fibrotic phase
  • Langerhans cells stain for CD1a, Langerin, and S100
Terminology
  • Eosinophilic granuloma, Langerhans cell granulomatosis, histiocytosis X ("H-X")
  • Multisystem diseases: Letterer-Siwi disease, Hand-Schüller-Christian disease, Hashimoto-Pritzker syndrome, where lung involvement is histologically indistinguishable from cellular phase of PLCH
Epidemiology
  • Uncommon, encompassing 3 - 5% of lung biopsies for interstitial lung disease
  • >90% of cases associated with smoking - considered a smoking related disease
  • Usually ages 20 - 50 years
  • More common in Caucasian than African Americans or Asians
Sites
  • 50% of cases only involve lung
  • 20% of those with multicentric disease (i.e. bone, skin, lymph nodes, spleen, CNS, pituitary, rarely thyroid and thymus) have lung involvement
Pathophysiology
  • Debatable as reactive versus neoplastic, could arise from smoking related and immunomodulatory processes (Arch Pathol Lab Med 2016;140:230)
  • PLCH may be a reactive process with a subset showing clonality, but extrapulmonary forms of Langerhans cell histiocytosis are thought to be neoplastic
  • Unpredictable course, even with smoking cessation: some spontaneously resolve, others remain stable, some progress to honeycomb fibrosis
Etiology
  • Disorder of cells with Langerhans cell phenotype
Clinical Features
  • Many patients asymptomatic
  • Chronic cough and exertional dyspnea typical (Eur J Intern Med 2015;26:351)
  • Rarely can present with hemoptysis
  • Recurrent spontaneous pneumothorax in 15 - 25% of cases
  • Pulmonary hypertension and vasculopathy frequent in advanced cases
  • Diabetes insipidus in 15% of patients from pituitary involvement
  • Generally restrictive features in early disease, obstructive features in late disease
  • Secondary malignant and non-malignant neoplasms
Diagnosis
  • Lung biopsy is necessary for a definitive diagnosis, although may not be required if imaging findings are highly characteristic (Orphanet J Rare Dis 2012;7:16)
  • Transbronchial biopsy may be diagnostic; otherwise, requires surgical lung biopsy
Laboratory
  • Normal peripheral eosinophil blood count
Radiology Description
  • Upper / middle lung predominance
  • X-ray: small nodules generally up to 1 cm and variably sized cysts
  • High resolution CT: bronchiolocentric stellate nodules possibly with surrounding ground glass opacities, some with faint lucent cavity
    • Advanced disease with cysts, emphysema adjacent to scarring, reticular and nodular opacities, honeycombing, can mimic IPF
  • FDG-PET may show increased uptake, especially in early nodular disease
Prognostic Factors
  • 10 - 20% may progress to respiratory failure
  • Median survival 12 years, 5 year survival 70%, 10 year survival 60%
  • Worse prognosis in cases with pulmonary hypertension
  • Worse prognosis for those with baseline poor respiratory function and those with concurrent neoplasms
  • Worse prognosis with extremes of age, prolonged constitutional symptoms, multiorgan involvement, extensive cysts, honeycomb changes
Case Reports
Treatment
  • Smoking cessation most effective
  • Corticosteroids +/- chemotherapeutic agents show mixed results
  • Lung transplantation in advanced cases
Gross Description
  • Upper lobe predominance, fine nodular infiltrate, with nodules up to 1.5 cm
  • Advanced disease with cysts, cavitary lesions, and honeycombing
Gross Images

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Tiny nodules

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Advanced

Micro Description
  • Early cellular phase and older fibrotic lesions may be intermixed, but one pattern typically predominates
  • Scattered, variably sized stellate nodules ("star fish-like" or "Medusa head-like") with interstitial scarring and aggregates of Langerhans cells
  • Layered appearance of nodules, bronchiolocentric distribution with pleural/subpleural sparing
  • Confluence of nodules → serpentine sheath around small airways
  • Langerhans cells are relatively large with abundant, granular, mildly eosinophilic and indistinct cytoplasm, grooved nuclei with indented nuclear membranes / grooves, "crumpled tissue paper" nuclear outlines, pale basophilic nucleus, one or two small nucleoli
  • Also prominent eosinophils, lymphocytes, plasma cells, activated macrophages, multinucleated giant cells
  • Variably sized cystic spaces at periphery of nodules lacking lining cells, secondary to traction on surrounding alveolar walls or airways
  • Frequent hemosiderin, necrosis, alveolar lining cell hyperplasia, pigmented alveolar macrophages ("smoker's macrophages")
  • Variable vasculitis, patchy organization, other smoking related changes such as emphysema, respiratory bronchiolitis, desquamative interstitial pneumonia
  • Older fibrotic lesions have fewer Langerhans cells and eosinophils, more fibrosis
  • May show pulmonary hypertension
  • Sarcomatous variant has significant atypia and mitotic figures
Micro Images

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Microcystic change

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End stage Langerhans'

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Kidney bean shaped nuclei

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Stellate nodules

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Pneumonia–like pattern

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Fibrotic nodule with histiocyte-like cells

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CD1a+

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CD1a, CD56, S100

Cytology Description
  • Langerhans cells with abundant cytoplasm and grooved nuclei with background eosinophils and lymphocytes
  • Bronchioalveolar lavage may show increased numbers (>5%) of CD1a+ Langerhans cells but test with low sensitivity (Respir Med 2012;106:1286)
Positive Stains
Electron Microscopy Description
  • Birbeck's granules (pentilaminar intracytoplasmic structures, tennis racket shaped)
Electron Microscopy Images

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Birbeck granules

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Binucleated Langerhans cells, orbit

Molecular / Cytogenetics Description
Differential Diagnosis