The patient improved on empiric NSAIDs and was discharge

1
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

2
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

3
4x
4
10x
5
20x
6
40x
7
CD1a
8
S100
9
PULMONARY LANGERHANS- CELL HYSTIOCYTOSIS

• Final Pathological Diagnosis

10
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 monocyte-macrophage lineage derived
  from bone marrow involved in antigen presentation
  in the tracheobronchial tree

11
Classification of Histiocytosis

• Single-organ involvement
• Lung (gt85 of lung involvement occurs in
  isolation)
• Bone
• Skin
• Pituitary
• Lymph Nodes
• Thyroid, Liver, Spleen, Brain
• Multisystem Disease
• Multiorgan disease with lung involvement
• Multiorgan disease without lung involvement
• Multiorgan histiocytic disorder

12
Historical Terms

• Hystiocytosis X
• Eosinophilic Granuloma
• Letter-Siwe disease
• A rare systemic aggressive disease seen in adults
• Hand-Schüller-Christian disease
• Triad of exopthalmos, central diabetes insipidus,
  and bone lesions

13
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

14
Epidemiology

• Precise incidence and prevalence is hard to
  define in this disease
• 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
• gt90 of PLCH patients are smokers

15
Proposed Pathogenesis of PLCH
Vassallo R et al. N Engl J Med 20003421969-1978
16
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

17
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

18
Clinical Presentation

• Cough (50-70)
• Dyspnea (30-50)
• Fever, weight loss, diaphoresis (20-30)
• Asymptomatic (25)
• Chest Pain (10)

19
Clinical Presentation

• Pneumothorax (10-20)
• Extrapulmonary disease (15)
• Pulmonary hypertension
• Respiratory failure
• Secondary malignancy
• Physical Exam and Laboratory findings are variable

20
Chest Radiography

• Symmetrical micronodular and Interstitial
  infiltration predominantly in the middle and
  upper lobes
• Increased lung volumes
• Rare alveolar infiltrates, hilar LAD, pleural
  effusion

21
(No Transcript)
22
Tissue Diagnosis

• Bronchoalveolar Lavage
• Transbronchial Biopsy
• Open vs. Thorascopic Lung Biopsy

23
(No Transcript)
24
Management

• Smoking Cessation
• Corticosteroids
• Chemotherapy
• Vinblastine, MTX, Cyclophosphamide, Etoposide
• 2-chlorodeoxyadenosine
• Immune modulation Etanercept
• Pleurodesis of pneumothoraces
• Serial TTE and PFTs to monitor progression

25
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

26
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

27
Dfdx of pleuropericarditis

• Viral / Acute idiopathic
• Drug-induced
• Collagen vascular Sarcoid, RF, Lupus
• Tuberculosis
• Malignancy
• Infarction pericarditis
• Uremia
• Atypical infections fungal

28
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

29
Dfdx of pleuropericarditis

• Viral / Acute idiopathic
• Drug-induced
• Collagen vascular Sarcoid, RF, Lupus
• Tuberculosis
• Malignancy
• Infarction pericarditis
• Uremia
• Atypical infections fungal

30
Dfdx of pleuropericarditis

• Viral / Acute Idiopathic
• Drug-induced
• Collagen vascular Sarcoid, RF, Lupus
• Tuberculosis
• Malignancy
• Infarction pericarditis
• Uremia
• Atypical infections fungal

31
Final Diagnoses

• Pulmonary Langerhans-Cell Histiocytosis,
• Acute Viral Plueropericarditis
• Active Tobacco Abuse
• Coronary Artery Disease
• COPD
• Essential HTN
• Anxiety / Dysthymia

32
CPC 9.12.08 Flowsheet
Active Tobacco Abuse
HTN
Age
CAD
PLCH
COPD
Diminished epithelial defenses and mucociliary
elevator
Chronic respiratory insufficiency, cough and
exercise intolerance
Viral respiratory pathogen?
Pleuropericarditis
Acute self-limited dyspnea and atypical chest
pain
Increased cough, Subjective chills
Acute phase reactants Platelets, Ferritin, ESR
Chronic illness Anemia of chronic disease and
low albumin
Dysthymia/Anxiety
33
Thank You!

• Dr. Martin Blaser
• Dr. Anthony Grieco
• Dr. Elvio Ardilles
• Dr. Jonathon Ralston
• Dr. Kristin Remus
• Dr. James Tsay
• Dr. Christina Yoon