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

PULMONARY LANGERHANS’- CELL HYSTIOCYTOSIS

Final Pathological Diagnosis

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

Classification of Histiocytosis

• Single-organ involvemento Lung (>85% of lung involvement occurs in isolation)o Boneo Skino Pituitaryo Lymph Nodeso Thyroid, Liver, Spleen, Brain

• Multisystem Diseaseo Multiorgan disease with lung involvemento Multiorgan disease without lung involvemento Multiorgan histiocytic disorder

Historical Terms

• Hystiocytosis X• Eosinophilic Granuloma• Letter-Siwe disease

o A rare systemic aggressive disease seen in adults

• Hand-Schüller-Christian diseaseo 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 diseaseo 1200 new cases per yearo 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

Vassallo R et al. N Engl J Med 2000;342:1969-1978

Proposed Pathogenesis of PLCH

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 (20-

30%)• Asymptomatic (25%)• Chest Pain (10%)

Clinical Presentation

• 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

o Vinblastine, MTX, Cyclophosphamide, Etoposide

o 2-chlorodeoxyadenosine• 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

• 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

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

Dfdx of pleuropericarditis

• 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

• Active Tobacco Abuse• Coronary Artery Disease• COPD• Essential HTN• Anxiety / Dysthymia

Active Tobacco Abuse

COPD

HTN

CAD PLCH

Age

Diminished epithelial

defenses and mucociliary

elevator

Viral respiratory pathogen?

Pleuropericarditis

Chronic respiratory insufficiency, cough

and exercise intolerance

Acute self-limited dyspnea and atypical chest

pain

Increased cough, Subjective chills

CPC 9.12.08 Flowsheet

Acute phase reactants: Platelets, Ferritin, ESR

Dysthymia/Anxiety

Chronic illness: Anemia of chronic disease and

low albumin

Thank You!

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