Respiratory Pathology

Bassam Mansour, MD, EDICM

Head, Pulmonary Division
The Lebanese University, Faculty of Medicine
Head, Pulmonary & Critical Care Medicine
Zahraa Hospital University Medical Center
Interstitial Lung Diseases
Sarcoidosis
 Definition

❖ It is a chronic, multisystem disorder of unknown origin,

characterized by a non caseating granulomatous
accumulation of T Lymphocytes, Mononuclear
phagocytes that leads to a derangement of the normal
architecture.
 Definition

❖ This granulomatous disease involves the lung and

intrathoracic lymph nodes in 90% of patients; but it can
virtually affect any organ.

❖ Skin & eye involvement are also common (20 - 30%).

❖ Clinically significant involvement of the spleen, liver,

heart, CNS, or bone is less common (2 - 7%).
 Clinical expression

❖ The clinical expression & course are heterogeneous:

❖ ⅓ are asymptomatic with incidental bilateral hilar adenopathy.
❖ Symptoms can wax & wane, & reflect the organ involved.
❖ The course is usually favorable with spontaneous remissions
occurring in 25-50% of cases
❖ The association of Erythema nodosum, polyarthritis, & fever
(Löfgren syndrome) portends an excellent prognosis, with high
rates ( 85%) of spontaneous remission.
 Clinical Expression & Prognosis
❖ The clinical expression & course are heterogeneous:
❖ Black race, bone involvement, lupus pernio (a disfiguring
nasolabial cutaneous lesions), chronic hypercalcemia, &
chronic pulmonary sarcoidosis are factors that portray a more
aggressive disease & poor prognosis.
❖ Ethnic, geographic, & genetic factors influence prognosis.
❖ Mortality rates at 5 years is 7% compared with 4% among age
and gender matched controls without sarcoidosis.
 Etiology

❖ The exact cause of Sarcoidosis is unknown.

❖ A variety of infectious & non-infectious etiologies are

implicated without a well documented proof.

❖ Evidence is for an exaggerated immune response to a

class of persistent antigens, foreign or self-antigens.
 Pathology
❖ The hallmark is the non-caseating (non-necrotizing)
granuloma composed of epithelioid cells &
multinucleated giant cells, surrounded by a cuff of
lymphocytes & plasma cells.
❖ Because mycobacterial & fungal infections can cause
nonnecrotizing granulomas (commonly they cause
caseating granulomas), special stains for acid fast bacilli
& fungi should be performed to exclude these infectious
etiologies.
 Pathology

❖Multinucleatedgiant-cell in the
center of a granuloma,
surrounded by lymphocytes and
mononuclear cells in the
periphery
 Pathology
❖ In the lungs, the granulomas are often situated in the
submucosa of bronchioles & along bronchovascular
bundles

❖ Exuberant granulomatous inflammation may infiltrate &

destroy the affected organs, leading to significant &
irreparable loss of function; in the lung, progression to
end-stage fibrosis (honeycomb lung) can occur.
 Laboratory
❖ Nonspecific:
❖ Hypercalcemia (1 - 4%) & hypercalciuria (15 - 40%) reflect the
enhanced production of 1,2-dihydroxycalciferol by the
granuloma.
❖ Serum angiotensin-converting enzyme (ACE) levels are
elevated in 30 to 80% of patients with sarcoidosis. False-
positive results are uncommon Increased serum ACE can occur
in other granulomatous processes.
 Imaging

❖Bilateral hilar & right

paratracheal adenopathies is a
classic radiographic feature in
more than two thirds of
patients

Stage I Sarcoidosis
 Imaging

❖Extensive cystic radiolucencies

(honeycombing) & fibrosis with
predilection for the upper lobes of
both lungs.
❖Linear fibrotic strands and volume
loss are noted throughout.
❖BHL is present.

Stage II Sarcoidosis
 Imaging
❖Parenchymal infiltrates in 25 -50%
❖Typically patchy & bilateral, with a
predilection for the mid & upper
zones
❖Multiple focal nodular or alveolar
opacities in the upper lobes may
mimic tuberculosis & fungal
pneumonia.
❖Cavitation & pleural effusions are
rare (2% of patients).
Stage II Sarcoidosis
 Imaging

❖With advanced disease, mycetomas,

bullous emphysema, & pulmonary
hypertension may be observed
❖Calcification of the adenopathies
can be seen in long-standing
sarcoidosis. Stage IV Sarcoidosis
 Imaging / Staging

❖Aradiographic staging was developed > 4 decades ago can

be useful prognostically:
➢Stage 0: normal
➢Stage I: BHL without lung infiltrates
➢Stage II: BHL & lung infiltrates
➢Stage III: Lung infiltrates without intrathoracic adenopathies.
➢Stage IV: Advocated by some investigators to define patients with
extensive destruction, fibrosis, & volume loss.
 Imaging / Staging
❖The staging system may be useful as a prognostic guide:
Spontaneous remissions occur in 60 - 90% of patients with
Stage I; 40 - 70% with stage II, & 10 - 20% with stage III.

❖Virtually all fatalities occur in patients with stage II, III, or IV

disease.

❖Spontaneous remissions in ~ 40% within the 1st 6 months.

 Imaging / CT Chest

❖ChestCT is far more sensitive than CXR in delineating

parenchymal details or detecting the extent of the
adenopathies.

❖Thin slice HRCT is > to conventional CT in depicting

parenchymal lesions & discriminating alveolitis from fibrosis.
 Imaging / CT Chest
❖Nodules in 80% represent aggregates of granulomas.
❖Thickening of bronchovascular bundles with a beaded
appearance, is a cardinal sign.
❖Groung glass opacities 16 – 83%
❖Progression of the sarcoid lung lesion may form
conglomerate masses, architectural distortion, & cystic
destruction
❖Cavitation is noted in 2.7% typically with advanced disease.
 Imaging / CT Chest

❖With advanced disease CT can show

areas of bronchial thickening &
consolidation, large cystic, bullous
changes, & distortion of the normal
architecture.
 Pulmonary Function Testing
❖ Restrictive physiology is observed in 30 - 60%.
❖ Airway obstruction, with reduced FEV1 and expiratory
flow rates in 9 to 40% reflects endobronchial
inflammation & parenchymal distortion.
❖ The DLCO is the most sensitive but the degree of
impairment is less severe than in IPF.
❖ Serial PFTs are important to follow the course of the
disease and assess response to therapy.
 Pathologic Diagnosis
❖ Bronchoscopy with TBBx is the preferred diagnostic
procedure.
❖ Diagnostic yields are up to 95% when several biopsies
are taken from different lobes.
❖ TBNA & mediastinoscopy can demonstrate mediastinal
or hilar non-caseating granulomas when TBBx is
unyielding.
❖ Surgical lung biopsies are rarely needed.
 Extrapulmonary Manifestations
❖ Adenopathies: The intrathoracic nodes are enlarged in
>75%; Peripheral adenopathies are also common. Unlike
tuberculosis they do not ulcerate. They are non tender &
have a firm consistency.
❖ Eye: ~ 25% & may lead to blindness. Most have anterior
uveitis & less have posterior uveitis. We note blurred
vision, tearing, & photophobia. Conjunctival involvement
is also common.
 Extrapulmonary Manifestations
❖ Skin: ~ 25%. Most commonly: plaques, maculo-papular
rash, subcutaneous nodules, & lupus pernio.
❖ Erythema nodosum (EN) is common but non specific. EN
in association with arthralgias & sustemic symptoms
does not require Rx.
❖ Lupus pernio is seen as indurated blue-purple lesions in
the nose, cheeks, knees, ears & fingers. The nasal
mucosa is involved & the underlying bone can be
destroyed.
 Extrapulmonary Manifestations
❖ Upper Respiratory Tract: Nasal mucosa is involved in ~
20% with stuffiness. Any structure of the mouth can be
affected. The larynx in 5% leading to hoarseness, stridor,
& even complete obstruction.
❖ Bone marrow & spleen: 15-40% but rarely cause
hematologic disturbances.
❖ Liver: >60% with clinically insignificant liver function
abnormalities. Hepatomegaly is seen in ~ 20% with a
mild cholestatic picture.
 Extrapulmonary Manifestations
❖ Kidney: clinically apparent involvement is rare. 1-2 %
have hypercalciuria. Nephrocalcinosis & nephrolithiasis
can occur associated with enhanced calcium absorption
in the gut due to high circulating 1-2-dihydroxyvit D.

❖ Nervous System: ~ 5% cranial nerve involvement with

facial palsy, optic nerve involvement, hearing
abnormalities, chronic meningitis, peripheral
neuropathies, psychiatric disorders…
 Extrapulmonary Manifestations
❖ Musculo-skeletal System: Joint involvement is common
in 25-50% with arthralgias & sometimes frank arthritis.
Bone lesions in 5% & include cystic lesions. These lesions
can be tender.

❖ Heart: ~ 5% have significant involvement with significant

LV dysfunction. Arrhythmias are frequent with
conduction abnormalities & sometimes heart blocks.
Percarditis & cor pulmonale are less frequent.
 Extrapulmonary Manifestations

❖ Endocrine: Complete hypopituitarism is rare, diabetes

insipidus is more common. Bone lesions in 5% & include
cystic lesions. These lesions can be tender.

❖ Exocrine: parotid enlargement is common, clinical

apparent in ~ 10%.

❖ GI: seen on autopsy, it is rarely clinically significant.

 Treatment
❖ Corticosteriods are the mainstay of Rx as they may
produce dramatic remissions in patients with severe or
progressive sarcoidosis.
❖ Favorable responses are achieved in 60 - 90%.
❖ Relapses occur in 16 - 74% after the cessation of Rx.
❖ Because of the potential for spontaneous resolution, the
toxicities associated with corticosteroid therapy,
indications for treatment can be controversial.
 Treatment
❖ Inhaled corticosteroids have minimal value as the
primary Rx for pulmonary sarcoidosis.
❖ Immunosuppressive Rx (methotrexate, azathioprine,
cyclosporine…) have been used, with anecdotal
successes.
❖ NSAIDs are effective in Rx of articular manifestations but
have no role in treating more severe cases of pulmonary
or extrapulmonary sarcoidosis.
 Treatment
❖ Antimalarial drugs (chloroquine & hydroxychloroquine)
have immunomodulating properties & concentrate in
the granuloma.
❖ Anecdotal responses noted in cutaneous, osseous, &
neurologic sarcoidosis & sarcoid induced hypercalcemia.
❖ A small randomized trial suggested benefit with
chloroquine: improved symptoms, PFT results, ACE
levels, & Ga67 scan.
 Treatment
❖ Given the potential serious ocular toxicity with
chloroquine, hydroxychloroquine, is preferred.
❖ The dose of hydroxychloroquine is 200 mg once or twice
daily for a 6-month trial.
❖ Long-term maintenance Rx (100 to 400 mg/d) is
reserved for patients with unequivocal responses.
❖ Slit-lamp examinations should be done to rule out ocular
toxicity.
Respiratory Pathology

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