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Usual interstitial pneumonia is the most common form of idiopathic
interstitial fibrosis (70% of all cases), and unfortunately carries a poor
prognosis.
This condition is characteristically most prominent subpleurally in the
lower lobes of the lung.
The most important histological feature is the highly
variegated lung architecture often including the entire spectrum from
normal alveolar walls to end stage fibrotic lesions (honeycomb) in the
same section.
[ Each of the terms usual interstitial pneumonia,
cryptogenic fibrosing alveolitis, and idiopathic pulmonary fibrosis
stresses certain features - the cause is unknown, alveolar inflammation is
an important part of the disease, fibrosis is the usual sequel, and there
may be unusual forms of interstitial pneumonia. ]
The clinical, radiologic
and functional features are those of restrictive lung disease.
The disease is usually diagnosed in the sixth decade.
Dyspnea of gradual onset, often over 5 to 10 years, is
customary.
Electron microscopic examination reveals gross
distortion and infolding of the alveolar basal lamina in the fibrotic
areas.
Loose granulation tissue in the alveolar spaces leads to alveolar collapse
and contraction of fibrous tissue.
About one quarter of all cases date their illness to an acute broncho-pulmonary infection, an observation that raises the possibility
that the disease is sequel to viral infection.
The classic auscultatory
finding consists of fine crackles at the lung bases in late inspiration.
The prognosis is bleak, with an average survival of 5 years.
The response to treatment, usually corticosteroids, is generally poor.
The etiology of usual interstitial pneumonia is not
known, but the condition is usually thought of as an immunologically
mediated disorder.
Evidence includes the association with
collagen-vascular disease and serum protein abnormalities, the presence of
circulating immune complexes, the presence of immunoglobulins in alveolar
walls, and the release of a lymphokine, migration inhibitory factor, when
lymphocytes of patients with the disease are exposed to collagen.
According to one theory, macrophages play a central
role in the pathogenesis of usual interstitial pneumonia, and the initial
damage is to collagen, by an unknown agent.
Macrophages engulf collagen
fragments and secrete a fibroblast-stimulating factor, thereby leading to
fibrosis.
They also release a chemotactic factor for polymorphonuclear
leukocytes, which then do further damage.
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A useful classification of usual interstitial pneumonia is as follows but
it should be recognized that the morphologic features are the same in
each:
- Usual interstitial pneumonia associated with collagen
vascular diseases. These include
rheumatoid arthritis, systemic lupus erythematosis, and progressive
systemic sclerosis. About 20% of cases of usual interstitial pneumonia
have overt evidence of a connective tissue disease.
- Usual interstitial pneumonia associated with serum
abnormalities but not with collagen vascular disease. These include
cryoglobulinemia, abnormal serum globulins, positive antinuclear
antibodies, and positive rheumatoid factor (rarely, positive in the
absence of rheumatoid arthritis). These abnormalities have been found in
up to 40% of cases.
- Usual interstitial pneumonia without overt evidence
of collagen vascular disease or serum abnormalities.
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Microscopic
features:
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Histologically, there is subpleural accentuation of the fibrotic
and inflammatory process with relative sparing of centri-acinar
structures.
The key morphologic feature of usual interstitial
pneumonia is heterogeneity of lesions, that is, different appearances in
different parts of the lung, in different lung biopsies, and even in
different fields of the same lung biopsy.
The variation is so great that
in some fields the alveolar walls are entirely normal.
Inflammation varies
from subtle increased cellularity (mainly lymphocytes) of otherwise
apparently normal alveolar walls to diffuse alveolar damage with obvious
alveolar wall inflammation and hyperplasia of type II cells.
Lymphoid
aggregates are also seen. By the time a lung biopsy is performed fibrosis
is always present, but its severity varies.
There may be subtle alveolar wall thickening, demonstrated only by special stains for collagen.
In other
cases fibrosis may be obvious but alveolar walls may be maintained,
although the acinar structure is somewhat simplified.
At the extreme is honeycomb lung, brought about by alveolar wall
inflammation and collapse.
Neutrophils are
not a prominent feature, except in the infected cystic spaces.
However,
the bronchoalveolar lavage fluid contains increased numbers of neutrophils.
The epithelial lining ranges from normal alveolar cells in
undamaged areas to large rounded hyperplastic type 2 cells in diseased
areas with focal ciliated columnar, goblet cells and occasionally squamous
metaplasia in severely affected areas.
In areas of advanced disease, most
of the fibrosis consists of eosinophilic collagen with scanty fibroblastic
cells.
The cystically dilated air spaces of contain inspissated mucus
admixed with histiocytes, inflammatory cells and cell debris.
As a result
of inflammation and scarring, there is also some bronchioloectasis which
is well recognized by the radiologists as "traction bronchiectasis".
UIP
is also characterized by the presence of “fibroblast foci”.
These
are areas of active disease, consisting of fibroblastic and myofibroblastic proliferation set in a myxoid background, which represent
organization of intra-alveolar exudates (ongoing fibrosis).
Fibroblast
foci are an important component of the temporal heterogeneity
characteristic of the disease process.
Inflammatory cellular infiltration
is usually mild, although focal lymphoid hyperplasia with prominent
lymphoid follicles may be present, particularly in cases associated with
systemic disease.
Reactive smooth muscle hyperplasia is often marked and
is particularly prominent around small bronchioles. The smooth muscle
fibers are of normal morphology, unlike those seen in
lymphangioleiomyomatosis
which is characterized by immature smooth muscle
proliferation.
Accumulation of tight clusters or loosely dispersed
macrophages within alveolar spaces is commonly seen in UIP, particularly
in cigarette smokers, and this DIP-like reaction in an otherwise typical
case of UIP shows no correlation with the stage of the disease.
Pulmonary arterial vascular changes are
often seen in fibrotic areas, but these are of little clinical
significance as there is no correlation between these changes and the
presence of
pulmonary hypertension.
Typically, UIP is characterized by the
absence of vasculitis , granulomata and asbestos bodies.
Pleural fibrosis is
very rare in UIP.
The presence of conspicuous asbestos bodies
should suggest
asbestosis
, which apart from the absence of asbestos
bodies and pleural disease, UIP otherwise resembles.
Idiopathic Pulmonary Fibrosis
;
Acute interstitial pneumonia (AIP)/organizing
diffuse alveolar damage DAD)
;
Respiratory bronchiolitis-interstitial lung
disease (RBILD);
Non-specific interstitial pneumonia (NSIP)
;
Desquamative interstitial pneumonia (DIP)
;
Lymphocytic Interstitial Pneumonia /
Follicular Bronchiolitis.
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Heterogeneous proliferation of type II pneumocytes in usual
interstitial pneumonia.Pathology.
2006 Oct;38(5):433-6.
AIMS:
Heterogeneous alveolar fibrosis, the most specific pathological
finding in idiopathic pulmonary fibrosis (IPF)/usual interstitial
pneumonia (UIP), enables differentiation of UIP from other
interstitial pneumonias. Heterogeneous and mild alveolar injury may
occur, and this will be a clue to clarifying the pathogenesis of UIP.
METHODS: We examined nine lung biopsy specimens obtained from patients
with IPF and five control specimens. We semi-quantitatively examined
alveolar injury by measuring the density of type II pneumocytes.
Serial 3 microm sections were stained with anti-Thomsen-Friedenreich (TF)
antibody. We divided each UIP lesion into three areas: area near
fibrosis (fibrous area), area with an apparently normal alveolar
structure (normal area), and area between the fibrous and normal areas
(intervening area). RESULTS: Immunostaining with anti-TF antibody
stained the apical surface of type II pneumocytes and enabled us to
recognise and count type II pneumocytes. The density of type II
pneumocytes was increased in the fibrous area, and gradually decreased
away from the fibrous lesion. The densities of type II pneumocytes in
the above three areas were, respectively: 13.9+/-2.0, 7.2+/-1.6, and
9.5+/-1.6/mm alveolar length. The densities in the fibrous and
intervening areas were significantly greater than those in the normal
area and in control specimens (6.6+/-0.7/mm). CONCLUSIONS: If the
density of type II pneumocytes indicates their degree of regeneration
after alveolar injury, it reflects the severity of the pre-existing
injury. This study confirms that heterogeneous and mild alveolar
injury occurs in UIP.
Histologic
features and pathologic diagnosis in usual interstitial pneumonia.
Zhonghua Bing Li Xue Za Zhi.
2004 Apr;33(2):105-8.
OBJECTIVE: To
study the pathologic features, differential diagnosis and role of open
lung biopsies (OLB) in usual interstitial pneumonia (UIP). METHOD: The
authors reviewed the pathologic, clinical and radiologic features of
five cases of UIP (one autopsy case and four OLB cases), with
follow-up information. RESULTS: The typical histologic features were a
non-uniform distribution of alveolar inflammation, fibroblastic foci,
interstitial fibrosis and honeycomb change. There also was associated
metaplasia of bronchiolar epithelium, type II pneumocyte hyperplasia
and accumulation of alveolar macrophages. CONCLUSIONS:
Characteristically, UIP exhibits temporal heterogeneity under
low-power light microscopy, which includes changes in both the early
and end stages. Open lung biopsy is an important diagnostic adjunct
for suitable patients with atypical radiologic features on
computerized tomography. Correlation between clinical, radiologic and
pathologic findings is also essential for a correct diagnosis.
BAL findings in
idiopathic nonspecific interstitial pneumonia and usual interstitial
pneumonia.Eur
Respir J. 2003 Aug;22(2):239-44.
Idiopathic
pulmonary fibrosis (IPF), which has the histological pattern of usual
interstitial pneumonia (UIP), is a progressive interstitial lung
disease with a poor prognosis. Idiopathic interstitial pneumonias with
a histological pattern of nonspecific interstitial pneumonia (NSIP)
have a better prognosis than UIP, and may present with a clinical
picture identical to IPF. The authors hypothesised that
bronchoalveolar lavage (BAL) findings may distinguish between UIP and
NSIP, and have prognostic value within disease subgroups. BAL findings
were studied retrospectively in 54 patients with histologically proven
(surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all
presenting clinically as IPF. These findings were also compared with
the BAL profile of patients with other categories of idiopathic
interstitial pneumonias. BAL total and differential cell counts did
not differ between the two groups. Survival was better in NSIP. In
neither group were BAL findings predictive of survival or changes in
lung function at 1 yr, even after adjustment for disease severity,
smoking and treatment. BAL differential counts in fibrotic NSIP
differed from respiratory bronchiolitis-associated interstitial lung
disease, but not from desquamative interstitial pneumonia or cellular
NSIP. The authors conclude that bronchoalveolar lavage findings do not
discriminate between usual interstitial pneumonia and nonspecific
interstitial pneumonia in patients presenting with clinical features
of idiopathic pulmonary fibrosis, and have no prognostic value, once
the distinction between the two has been made histologically.
Usual
interstitial pneumonia: histologic study of biopsy and explant
specimens. Am
J Surg Pathol. 2002 Dec;26(12):1567-77.
The pathologic
findings in biopsy and subsequent explant specimens from 20 patients
with usual interstitial pneumonia (UIP) were reviewed to refine
histologic criteria for diagnosis, to identify factors that may
confound diagnosis, and to assess the relationship of UIP and
nonspecific interstitial pneumonia (NSIP). One case of NSIP was also
identified and included for comparison. Surgical biopsies from 15 of
the 20 UIP cases were diagnosed as UIP, whereas 5 showed only
nondiagnostic changes. An important new observation is that areas
resembling nonspecific interstitial pneumonia (NSIP-like areas) are
present in the majority of UIP cases in both biopsy and explant
specimens, and they are extensive in some. Ten of the 15 UIP biopsies
were considered straightforward, with typical patchy interstitial
fibrosis, honeycomb change, and fibroblast foci. Five cases were
considered difficult because of prominent NSIP-like areas in two,
extensive honeycomb change in one, superimposed diffuse alveolar
damage in one, and superimposed bronchiolitis obliterans-organizing
pneumonia in one. The most helpful feature for diagnosing UIP in
difficult cases was the presence of a distinct patchwork appearance to
the characteristic uneven or variegated parenchymal involvement along
with evidence of architectural derangement. No explant showing UIP was
preceded by biopsy findings of NSIP, and the one NSIP case appeared
similar at biopsy and explant. NSIP or NSIP-like areas and UIP may
reflect different mechanisms of fibrosis related either to different
severity of injury or to different injuries.
Histopathologic
variability in usual and nonspecific interstitial pneumonias.
Am J Respir Crit Care Med. 2001 Nov 1;164(9):1722-7.
Findings of
surgical lung biopsy (SLB) are important in categorizing patients with
idiopathic interstitial pneumonia (IIP). We investigated whether
histologic variability would be evident in SLB specimens from multiple
lobes in patients with IIP. SLBs from 168 patients, 109 of whom had
multiple lobes biopsied, were reviewed by three pathologists. A
diagnosis was assigned to each lobe. A different diagnosis was found
between lobes in 26% of the patients. Patients with usual interstitial
pneumonia (UIP) in all lobes were categorized as concordant for UIP (n
= 51) and those with UIP in at least one lobe were categorized as
discordant for UIP (n = 28). Patients with nonspecific interstitial
pneumonia (NSIP) in all lobes were categorized as having fibrotic (n =
25) or cellular NSIP (n = 5). No consistent distribution of lobar
histology was noted. Patients concordant for UIP were older (63 +/- 9
[mean +/- SD] yr; p < 0.05 as compared with all other groups) than
those discordant for UIP (57 +/- 12 yr) or with fibrotic NSIP (56 +/-
11 yr) or cellular NSIP (50 +/- 9 yr). Semiquantitative
high-resolution computed tomography demonstrated a varied profusion of
fibrosis (p < 0.05 for all group comparisons), with more fibrosis in
concordant UIP (2.13 +/- 0.62) than in discordant UIP (1.42 +/- 0.73),
fibrotic NSIP (0.83 +/- 0.58), or cellular NSIP (0.44 +/- 0.42).
Survival was better for patients with NSIP than for those in both UIP
groups (p < 0.001), although survival in the two UIP groups was
comparable (p = 0.16). Lobar histologic variability is frequent in
patients with IIP, patients with a histologic pattern of UIP in any
lobe should be classified as having UIP.
Bronchiolitis
obliterans and usual interstitial pneumonia. A comparative
clinicopathologic study.Am
J Surg Pathol. 1986 Jun;10(6):373-81.
The clinical,
radiographic, and pathologic features were studied in 24 cases of
bronchiolitis obliterans and 16 cases of usual interstitial pneumonia,
to define better their distinguishing characteristics. Bronchiolitis
obliterans had a more acute onset often associated with fever, while
the presentation of usual interstitial pneumonia was insidious with
dyspnea and cough. The radiographs in usual interstitial pneumonia
uniformly showed bilateral interstitial opacities, while they were
more variable in bronchiolitis obliterans, with air space densities in
15 and interstitial opacities in nine. Prognosis was considerably
better for bronchiolitis obliterans patients. Resolution of disease
occurred in nearly half, while no patient with usual interstitial
pneumonia recovered. Three individuals with bronchiolitis obliterans
(12.5%) died of progressive disease, compared to 10 with usual
interstitial pneumonia (62.5%). Pathologically, the lesion in
bronchiolitis obliterans affected mainly air spaces in a
peribronchiolar distribution, while the changes in usual interstitial
pneumonia were mainly interstitial and randomly distributed. The
fibrosis in bronchiolitis obliterans was composed of proliferating
fibroblasts, compared to collagen deposition in usual interstitial
pneumonia. These findings emphasize that bronchiolitis obliterans and
usual interstitial pneumonia represent separate and distinct
clinicopathologic entities.
Morphological definition of a case of 'usual' interstitial pneumonia. Cytobios.
1979;26(102):131-5.
A
61-year-old Caucasian female complained of shortness of breath, fever,
and a period of rapid weight loss. After routine studies, the patient
underwent an open lung biopsy in order to define the characteristics
of the interstitial lung disease, and initiate appropriate therapeutic
intervention. Typical fibrotic and cellular proliferation were evident
in the parenchyma, as determined by standard light microscopy.
However, in a correlated study using light microscopy of plastic
embedded tissue, as well as scanning and transmission electron
microscopy, a major proliferating cell type was identified as a type
II pneumocyte. These cells were the predominant lining cells of the
alveoli and clearly protruded into and limited available respiratory
air spaces. The predominance of type II pneumocytes in the
pathogenesis of certain respiratory diseases requires that a better
explanation be sought for this phenomenon.
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