Transcript Document

Interval History
• The patient was admitted to respiratory
isolation to rule out active infection with
Mycobacterium Tuberculosis
• Acid-fast bacilli culture and smear were
negative
• The patient improved on empiric NSAIDs
and was discharged home
• The patient returned to her baseline
exercise tolerance and was asymptomatic
within 1 week
Interval History
• Repeat CT imaging showed resolution of
effusions, but persistent nodules,
concerning for metastatic disease of
unknown primary
• PET Scan and Abdominal CT scans did not
show evidence of extrapulmonary
malignancy
• The patient returned two months later for a
thorascopy with lung wedge resection of a
characteristic nodule
4x
10x
20x
40x
CD1a
S100
Final Pathological Diagnosis
PULMONARY
LANGERHANS’- CELL
HYSTIOCYTOSIS
PLCH: Introduction
• Histiocytosis encompasses a group of
diverse disorders with the common
primary event of the accumulation and
infiltration of monocytes, macrophages,
and dendritic cells in the affected tissues
• Langerhans Cells are a dendritic cell
subtype and part of the monocytemacrophage lineage derived from bone
marrow involved in antigen presentation in
the tracheobronchial tree
Classification of Histiocytosis
• Single-organ involvement
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o
o
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Lung (>85% of lung involvement occurs in isolation)
Bone
Skin
Pituitary
Lymph Nodes
Thyroid, Liver, Spleen, Brain
• Multisystem Disease
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Multiorgan disease with lung involvement
Multiorgan disease without lung involvement
Multiorgan histiocytic disorder
Historical Terms
• Hystiocytosis X
• Eosinophilic Granuloma
• Letter-Siwe disease
o
A rare systemic aggressive disease seen in
adults
• Hand-Schüller-Christian disease
o
Triad of exopthalmos, central diabetes
insipidus, and bone lesions
Langerhans Cells
• Discovered by Paul
Langerhans in 1868
• The hallmark
ultrastructural feature
called the Birbeck
Granule discovered in
1961
• The CD1a cell surface
antigen distinguises
LC from other
histiocytes
Epidemiology
• Precise incidence and prevalence is hard
to define in this disease
o
o
1200 new cases per year
0.5-5.4 cases / million
• 5% of lung-biopsy specimens in patients
with ILD result in PLCH
• No known genetic susceptibility
• Mainly in caucasians. Male to female
ratio is changing over the decades…
• >90% of PLCH patients are smokers
Proposed Pathogenesis of PLCH
Vassallo R et al. N Engl J Med 2000;342:1969-1978
Reactive vs. Neoplastic?
• Spontaneous
remission
• Abscence of
chromosomal
abnormalities
• Overall good
prognosis in majority
of cases
• Monoclonal
proliferation in
extrapulmonary tissue
• Infiltration of aberrent
cells into normal
tissue
• Response to
chemotherapy and
possible fatal outcome
in more severe cases
Histopathological Features
• Proliferation of Lagerhans Cells along the
small airways serves as the nidus of
cellular/fibrotic nodules from 5mm to 1.5 in
size. Eosinophils may be present
• In severe disease, nodules may interconnect
and cavitate to produce distinctive
honeycomb-like structures
• Given that most patients are smokers,
concominant COPD and ILD 2/2 respiratory
bronchiolitis is often present
Clinical Presentation
• Cough (50-70%)
• Dyspnea (30-50%)
• Fever, weight loss, diaphoresis (2030%)
• Asymptomatic (25%)
• Chest Pain (10%)
Clinical Presentation
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Pneumothorax (10-20%)
Extrapulmonary disease (15%)
Pulmonary hypertension
Respiratory failure
Secondary malignancy
• Physical Exam and Laboratory findings
are variable
Chest Radiography
• Symmetrical
micronodular and
Interstitial infiltration
predominantly in the
middle and upper
lobes
• Increased lung
volumes
• Rare: alveolar
infiltrates, hilar LAD,
pleural effusion
Tissue Diagnosis
• Bronchoalveolar Lavage
• Transbronchial Biopsy
• Open vs. Thorascopic Lung
Biopsy
Management
• Smoking Cessation
• Corticosteroids
• Chemotherapy
Vinblastine, MTX, Cyclophosphamide,
Etoposide
o 2-chlorodeoxyadenosine
o
• Immune modulation: Etanercept
• Pleurodesis of pneumothoraces
• Serial TTE and PFTs to monitor
progression
Prognosis
• For a majority of patients, the disease
regresses with smoking cessation
• It is not known to predict those who tend
to progress, although age, prolonged
constitutional symptoms, extrapulmonary
involvement, abnormal PFTs are markers
of poor outcome
Back to our case…
• This patient has baseline respiratory
insufficiency 2/2 PLCH and COPD, but
presented with an acute respiratory illness
not characteristic of these diagnoses
• She endorsed chills, dyspnea, and chest
pain. There was radiographic evidence of
pleuropericarditis which symptomatically
and radiographically improved within 1-2
weeks on NSAIDs
Dfdx of pleuropericarditis
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Viral / Acute idiopathic
Drug-induced
Collagen vascular: Sarcoid, RF, Lupus
Tuberculosis
Malignancy
Infarction pericarditis
Uremia
Atypical infections: fungal
Follow-up
• Pleural fluid was negative for Acid-Fast,
Bacterial or Fungal organisms
• HIV Negative
• The patient continues to struggle with
smoking cessation and reports baseline
shortness of breath and cough
• The patient reports an increase in
smoking because of the anxiety of
“having cancer”
• Steroids have not been offerred due to
the relatively mild course of her disease
Dfdx of pleuropericarditis
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Viral / Acute idiopathic
Drug-induced
Collagen vascular: Sarcoid, RF, Lupus
Tuberculosis
Malignancy
Infarction pericarditis
Uremia
Atypical infections: fungal
Dfdx of pleuropericarditis
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Viral / Acute Idiopathic
Drug-induced
Collagen vascular: Sarcoid, RF, Lupus
Tuberculosis
Malignancy
Infarction pericarditis
Uremia
Atypical infections: fungal
Final Diagnoses
• Pulmonary Langerhans’-Cell Histiocytosis,
• Acute Viral Plueropericarditis
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Active Tobacco Abuse
Coronary Artery Disease
COPD
Essential HTN
Anxiety / Dysthymia
CPC 9.12.08 Flowsheet
HTN
Age
CAD
Chronic respiratory
insufficiency, cough
and exercise
intolerance
Active Tobacco
Abuse
PLCH
COPD
Diminished
epithelial
defenses and
mucociliary
elevator
Viral respiratory
pathogen?
Pleuropericarditis
Acute self-limited Increased cough,
Acute phase reactants:
dyspnea and
Subjective chills
Platelets, Ferritin, ESR
atypical chest
pain
Chronic illness: Anemia
of chronic disease and
low albumin
Dysthymia/Anxiety
Thank You!
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Dr. Martin Blaser
Dr. Anthony Grieco
Dr. Elvio Ardilles
Dr. Jonathon Ralston
Dr. Kristin Remus
Dr. James Tsay
Dr. Christina Yoon