Smoking Induces the Accumulation of Langerhans Cells in the Lungs
Cell – Dendritic Cell
Langerhans Dendritic Macrophage Ashley Davidoff MD TheCommonVein.net
Langerhans Cells ? Dendritic Cells
Pulmonary Langerhans cell histiocytosis.). (c) Irregular nuclear groove with abundant cytoplasm of Langerhans cells (Papanicolau stain, ×1000) (insert. CD1a).
Courtesy IMAGES IN CYTOPATHOLOGY Myunghee Kang et al Cytologic features of pulmonary langerhans cell histiocytosis in bronchial washing: A report of two cases
Langerhans Cell Histiocytosis Langerhans Cell is a dendritic white cell with a wavy nucleus that creates granulomas and infiltrates the interstitium. It thus causes spiculated nodules that appear as spiculated nodules on CT Ashley Davidoff TheCommonVein.net
Smoking in Two Puff Harmony From the series “People of Israel” Ashley Davidoff MD TheCommonVein.net
Membranous airways (respiratory bronchiole, alveolar ducts, alveolar sacs) At the level of the membranous airways the effect is predominantly related to the loss of elasticity, and aberrant accumulation of smoking related macrophages. The weakening and destruction results in emphysema and the abnormal accumulation of smoking related macrophages relates to DIP Ashley Davidoff TheCommonVein.net
The Bronchocentric Nodule
Image a shows a normal bronchiole. Smoking excites the Langerhans cell which in turn induces attracts early cellular interstitial infiltrates of surrounding the bronchiole (b) including lymphocytes, macrophages, eosinophils, plasma cells, and fibroblasts. The cellular infiltrate progresses in a peribronchial pattern with mass effect on the bronchiole which becomes narrowed (c) and eventually disappears, a nodules of varying size manifest in the bronchiole pathway, sometimes round but often spiculated as the inflammatory reaction extends into the interstitium (d) The wall of the bronchiole breaks down and the cellular infiltrate may undergo necrosis resulting in thick walled cavities, sometimes round in shape (e) and sometimes with bizarre shapes (f) Eventually the inflammation recedes and a thin walled cyst remains (g ,h) Ashley Davidoff MD TheCommonVein.net
Langerhans Cells Attract Other Inflammatory cells and Surround the Bronchiole
Bronchocentric Langerhans Nodules Proliferation of the Langerhans Cell induces other cells to join causing a significant reaction around the bronchus with the inflammatory reaction extending into the interstitium and accounting for the stellate appearance Pulmonary Langerhans Cell Histiocytosis: An Update From the Pathologists’ Perspective March 2016 Archives of Pathology & Laboratory Medicine 140(3):230-240 Authors: Anja C Roden Eunhee S Yi
Florid Early Phase
Bronchocentric Nodules = Inflammatory Changes Around the Bronchus
Smoking excites the Langerhans cell which in turn induces and attracts early cellular interstitial infiltrates which surround the bronchiole. The diagram shows a bronchiole surrounded by an acute cellular inflammatory response Ashley Davidoff MD TheCommonVein.net lungs-0722
CT shows extensive disesae that appears to be centered around the bronchioles and small airways associated with centrilobular nodules, bronchiolectasis and thick walled cysts, more prominent in the upper lobes and mid lung fields but also involving the bases Ashley Davidoff MD TheCommonVein.net 50F 001b
Tree in Bud and Peribronchial Nodules with a Hint of Central Cavitation ie Bronchocentricity
As the inflammatory response progresses it has mass effect on the bronchiole causing the bronchiole to become narrowed. Ashley Davidoff MD TheCommonVein.net lungs-0723
CT shows extensive disease that appears to be centered around the bronchioles and small airways associated with centrilobular nodules, bronchiolectasis and thick walled cysts, more prominent in the upper lobes and mid lung fields but also involving the bases Ashley Davidoff MD TheCommonVein.net 50F 001
The inflammatory response is often aggressive and may infiltrate the surrounding interstitium resulting in a spiculated appearance. As the inflammatory response progresses it has mass effect on the bronchiole causing the bronchiole to become narrowed. Ashley Davidoff MD TheCommonVein.net lungs-0723b
Stellate Appearance Because of Infiltration of the Inflammatory Process into the Interstitium
It may become a Solid Nodule as It Obliterates the Lumen
As the inflammatory response progresses it has mass effect on the and may eventually occlude the bronchiole becoming a nodule. Ashley Davidoff MD TheCommonVein.net lungs-0724b
The inflammatory response is often aggressive and may infiltrate the surrounding interstitium resulting in a spiculated appearance Ashley Davidoff MD TheCommonVein.net lungs-0724
Figure 9. Nodular infiltrates with a stellate border extending into the surrounding interstitium in a patient with PLCH. (Courtesy of Professor A. Pesci, University of Parma.)
Spiculated Nodule of Langerhans Cell Histiocytosis TheCommonVein.net
Wall Starting to Break Down Creating a Thick Walled Cyst
The wall of the bronchiole breaks down and the cellular infiltrate may undergo necrosis resulting in thick -walled cavities, sometimes round in shape. Ashley Davidoff MD TheCommonVein.net lungs-0725
Sometimes with Bizarre Shapes
The wall of the bronchiole breaks down and the cellular infiltrate may undergo necrosis resulting in thick -walled cavities, sometimes bizarre in shape. Ashley Davidoff MD TheCommonVein.net lungs-0726
CT shows extensive disease that appears to be centered around the bronchioles and small airways associated with centrilobular nodules, bronchiolectasis and thick walled cysts, more prominent in the upper lobes and mid lung fields but also involving the bases Ashley Davidoff MD TheCommonVein.net 50F 001
Thick Walled Cysts = Thick Walled Dilated Small Airways
CT AXIAL VIEW – APEX SHOWS MOST SEVERE DISEASE LANGERHANS HISTIOCYTOSIS 53-year-old female with nicotine dependence presents with dyspnea and cough CXR (PA and Lateral) shows bilateral and extensive reticular nodular changes slightly more prominent in the upper lung zones CT scan from 16 months prior showed multiple relatively thick-walled cysts predominantly in the upper lobes. The cysts are round and air filled large and are between 5mm-8mm CT scan 9 months later shows improvement in the thickened walls of the cysts but maintenance of diffuse cystic changes predominantly in the upper lobes A CT scan done 2 years later shows no significant change in the diffuse bilateral cystic changes, dominant in the upper lobes and consistent with Langerhans histiocytosis Ashley Davidoff MD
With Time Inflammation Settles and There is Thinning of the Walls of the Cysts
As the inflammatory response subsides, thin-walled cavities evolve. Ashley Davidoff MD TheCommonVein.net lungs-0728b -hi res
As the inflammatory response subsides, thin-walled cavities evolve, sometimes bizarre in shape. Ashley Davidoff MD TheCommonVein.net lungs-0728b
Pulmonary Langerhans Cell Histiocytosis Thin Walled Bizarre Shaped Upper Lobe Cysts Ashley Davidoff MD TheCommonVein.net
CT scans show multiple thin walled cysts among a left upper lobe nodule and a thick walled cyst in the left apex Ashley Davidoff MD TheCommonVein.net adeno ca 007
In a Nutshell
Unknown Etiology
Strong association with smoking
Isolated to lungs
can affect multiple organs
20-40 years
M.F =1:1
Can present with PTX (10-25% spontaneous)
Location
smokers therefore
upper mid lung involvement-
lower lobe sparing
costophrenic sparing
can affect bone
nodules
irregular margins
random
decrease as disease progresses
cysts
thin walls
rounded
irregular bizarre
progress s disease progresses
ambivalent nature
Can get very sick needing lung transplant
steroid
cytotoxic drugs
lung transplant
Can resolve spontaneously
Stop smoking can resolve
Definition
Pulmonary Langerhans cell histiocytosis (PLCH)
(previously called eosinophilic granuloma of the lung, pulmonary Langerhans cell granulomatosis, and pulmonary histiocytosis X,
is
a cystic interstitial lung disease
Cause and predisposing factors
almost exclusively in cigarette smokers.
Caucasian young adults (20-40 years of age).
Structures involved
small airways terminal bronchioles and
infiltration into the interstitium
no to
Pathophysiology –
Result
25% can be asymptomatic and resolve spontaneously
Clinical
Sx
fever, fatigue, night sweats, anorexia, weight loss) and hemoptysis
10% of cases, PLCH presents with
spontaneous pneumothorax, which can be bilateral or recurrent
Extra pulm manifestations
bone lesions (skull, ribs, and pelvis)
pituitary involvement producing diabetes insipidus,
skin lesions
Imaging
Spiculated Nodule of Langerhans Cell Histiocytosis TheCommonVein.net
Langerhans Cell Histiocytosis Langerhans Cell is a dendritic white cell with a wavy nucleus that creates granulomas and infiltrates the interstitium. It thus causes spiculated nodules that appear as spiculated nodules on CT Ashley Davidoff TheCommonVein.net
nodular or reticulonodular opacities
middle and upper lung zones
sparing of the
bases
costophrenic angles
nodules
cavitating nodules
thick walled cysts
thin walled bizarre shaped cysts
preservation of lung volume
Hilar or mediastinal adenopathy is rare
Pleural thickening or effusion is rare
Honeycombing in advanced disease
FDG-PET scan
early in the course of disease (nodular phase)
may show increased uptake in the lungs
PFT
reduction in DLCO.
total lung capacity and expiratory flow rates are well-preserved
Restrictive, obstructive, and mixed patterns have
been described
BAL
Bx
Path
Early
cellular interstitial infiltrates of
Langerhans? cells,
Staining with antibodies against CD1a antigen on the cell surface
lymphocytes,
macrophages,
eosinophils, plasma cells, and fibroblasts
Mid stages
infiltrates enlarge to form nodules centered on small airways (peribronchial)
often stellate in configuration
Cavitation
Cyst Formation Initially Thick Walled
Then Thin Walled Cysts
CT UPPER LUNG ZONE PROMINENCE OF SMALL THIN WALLED CYSTS LANGERHANS HISTIOCYTOSIS 28 -year-old male with only minimal reported nicotine dependence presents with dyspnea and cough CXR (PA and Lateral) shows no acute cardiopulmonary disease with mild interstitial prominence CT scan showed multiple small cysts predominantly in the upper lobes. The cysts are round and air filled large and are between 5mm-8mm These findings are consistent with Langerhans histiocytosis though the relatively minor smoking history was inconsistent with the diagnosis and thus the person was subjected to multicentric wedge biopsies. Pathology revealed numerous stellate nodules which suggested ?burnout pulmonary Langerhans cell histiocytosis though immunostains including Langerin, CD1a and S100 were negative thus failing to confirm the diagnosis Other findings of histiocytic aggregates raised the possibility of an inhalational hypersensitivity pneumonitis. Ashley Davidoff MD
Next Phase
Cavitation within nodules due to
either an airway remnant or
de novo cavitation due to an enlarging
inflammatory infiltrate
Figure 2. Pulmonary Langerhans cell histiocytosis. Multiple nodules and cysts seen on computed tomography (CT) imaging ( A ) with histology showing cellular nodules ( B ), some with central cavities ( B , *) containing diagnostic Langerhans cell aggregates highlighted by positive immunohistochemical staining for CD1a ( C , brown stain ) typical of the early cellular stage of the disease. Coronal CT image from another patient showing multiple bizarre-shaped cysts in an upper-zone?predominant distribution, with sparing of the costophrenic angles representative of later-stage disease ( D ). Histologic features typical of later disease stages include cystic spaces ( E ) associated with paucicellular stellate fibrosis ( E , arrow ). Accumulations of smoking-related pigmented macrophages ( F , arrowhead ) are frequently seen in the surrounding parenchyma. Original magnifications: 2 3 ( E ); 4 3 ( B ); 40 3 ( C ); 100 3 ( F ).Gupta et al Diffuse Cystic Lung Disease: Part I American Journal of Respiratory and Critical Care Medicine 191(12) April 2015
Costophrenic Sparing
Costophrenic Sparing Ashley Davidoff MD TheCommonVein.net
Costophrenic Sparing Ashley Davidoff MD TheCommonVein.net
66M-Langerhans-019b-CT-upper-lones-cysts.jpg
Costophrenic Sparing Ashley Davidoff MD TheCommonVein.net
Sclerotic Bone Disease
66M-Langerhans-023-CTblastic-foci.jpg
Sclerotic Bone Disease possibly related to Pulmonary Langerhans Cell Histiocytosis but may just be a benign bone island Ashley Davidoff MD TheCommonVein.net
End-stage
prominent fibrotic scars and Langerhans cells absent
Clinical dyspnea or non-productive cough fatigue weight loss pleuritic pain- some asymptomatic
Some affected people recover completely after cessation of smoking,
complications such as pulmonary fibrosis and pulmonary hypertension .
Imaging
References and Links
Abbott G, et al Pulmonary Langerhans Cell Histiocytosis From the Archives of the AFIP RadioGraphics Vol. 24, No. 3 2004
Attili, A.K etal Smoking-related Interstitial Lung Disease: Radiologic-Clinical-Pathologic Correlation RadioGraphics Vol. 28, No. 5
Gupta et al Diffuse Cystic Lung Disease: Part I American Journal of Respiratory and Critical Care Medicine 191(12) April 2015
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