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Pulmonary Pathology Online
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Non-Neoplastic Pulmonary Diseases
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Neoplastic Pulmonary Diseases.
Presence of
granulomas in a lung biopsy or at autopsy is a relative common finding.
The differential
diagnosis range from sarcoidosis or tuberculosis to various rare
conditions.
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The patient’s
history , clinical findings and radiology is essential for making a
complete diagnosis.
A granuloma has been defined by Adams as
"a compact (organized) collection of mature mononuclear phagocytes
(macrophages and/or epitheloid cells) which may or may not be
accompanied by features such as necrosis or the infiltration of
inflammatory leucocytes".
Granulomas often arise in circumstances
where a stimulating agent persists in the host, resisting the usual
mechanisms of removal.
The most common example is the chronic
foreign body granuloma, but most granulomatous diseases involve
granulomas which comprise mostly epithelioid macrophages, with variable
numbers of macrophage giant cells.
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Many of these granulomas are immune
system driven and are a manifestation of a delayed Type IV
hypersensitivity reaction.
The compact or organized
arrangement of the macrophages in the granuloma is an an important
indicator. A few
macrophages lying together in close proximity should not be interpreted
as a granuloma.
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Other conditions
are as follows:
Wegener’s granulomatosis
Granulomas in Pneumoconiosis
(granulomas are main histological features)
- Includes
Talcosis and
- Berylliosis
Sarcoid-like reactions to tumours
Necrotizing sarcoidal granulomatosis (granulomas are main features)
Drug Reaction (Methotrexate)
IV
Talcosis
in drug abusers (granulomas are main histological features)
Other foreign body reactions (include aspiration pneumonia, in
haemosiderosis and pulmonary veno-occlusive disease).
Eosinophilic Granuloma(granulomas are a small component)
Bronchocentric granulomatosis (granulomas are a small component)
Churg-Strauss Syndrome
Lymphocytic Interstitial Pneumonitis
Amyloidosis (tumour) (granulomas
are a small component of the lesion)
Nodular Pulmonary Amyloid (Amyloidoma). |
Several
conditions
may have granulomas of some sort as part of their histological picture.
Many of these, such as drug reaction, is
diagnosed on the basis
of clinical history, as well as the accompanying histological features.
Examination under polarized light may allow foreign material such as
talc to be detected, but inclusions (Schaumann, conchoidal and asteroid
bodies) seen in the giant cells in granulomas may also polarize.
These inclusions are neither specific to nor diagnostic
of, sarcoidosis.
Granulomas related to identifiable
foreign material and situated around bronchioles suggest inhalation of
dust or other material while a vascular distribution is seen in IV talcosis in drug
abusers.
Granulomas may also be related to other exogenous factors such
as inhaled non-refractile foreign material or aspirated food particles,
or to endogenous deposition of amyloid or hemosiderin (as seen in
hemosiderosis or pulmonary veno-occlusive disease).
In these conditions
the diagnosis will usually be made on the basis of other features
present.
Necrotizing sarcoidal granulomatosis (NSG) is a rare disease
characterized by masses of sarcoid-like granulomas
associated with extensive geographic tissue necrosis and granulomatous
vasculitis.
Granulomas may be seen in bronchocentric granulomatosis (BCG) and in the
Churg-Strauss syndrome (CSS: asthma, peripheral blood eosinophilia and
systemic vascularity), but, both are very rare conditions, and there are
other major clinical and histological features, to establish the correct
diagnosis.
In BCG acute and chronic inflammation
destroys airways and palisaded histiocytes surround the central necrotic
tissue.
Eosinophils are abundant and the setting is often an asthmatic
patient with allergic bronchopulmonary
aspergillosis .
Scattered discrete granulomas may also be seen in the inflammatory mass lesion.
The BCG is
also seen in non-asthmatics, when it poses even more of a diagnostic
challenge and distinction from infection can be difficult , and a
similar reaction (unrelated to aspergillus sensitivity) may be seen
distal to obstructing bronchial tumor.
In CSS, necrotizing and
non-necrotizing granulomas are part of a range of pathological features,
which may exist in variable combination.
Wegener’s granulomatosis (WG)
is much commoner than BCG or CSS and thus worthy of more consideration.
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The characteristic necrotizing vasculitis and tissue necrosis are often
associated with a vaguely granulomatous inflammation with small, smudgy
multinucleate giant cells.
Sarcoid-like non-necrotizing granulomas are
very rare in WG, but the necrotizing granulomatous inflammation may be
confused with infection.
Distinction between
Wegener’s granulomatosis (WG) and infection:
(1)
lack of
positive staining for microorganisms in WG.
(2) the necrotizing vasculitis in WG will be found in
pulmonary vessels, away from the necro-inflammatory masses, surrounded by
normal lung. Rarely, alveolar walls show capillaries with small
collection of neutrophils within the alveolar interstitium. In contrast,
the vasculitis in infection is seen within areas of florid inflammation
or necrosis.
Pathological diagnosis of granulomatous lung disease: a review.
Histopathology.
2007 Feb;50(3):289-310.
Granulomas in
the lung are common diagnostic problems encountered by
pathologists. They occur in a wide range of pulmonary conditions,
ranging from common entities to uncommon ones and including both
infections and non-infectious diseases. This review summarizes the
main histological features that help distinguish various
granulomatous lung diseases. It concentrates on the most important
and common entities that may be encountered and emphasizes helpful
features in the differential diagnosis.
Pulmonary
granulomatous inflammation: From sarcoidosis to tuberculosis.
Semin Respir Infect. 2003 Mar;18(1):23-32
Granulomatous inflammation of the lung is characterized by the
recruitment and organization of activated macrophages and
lymphocytes in discrete lesions laced in a network of matrix
proteins. These lesions, termed granulomas, represent an important
defense mechanism against infectious organisms such as fungi and
mycobacteria, but also can be elicited by noninfectious agents.
Occasionally, this inflammatory reaction can develop for unknown
reasons, causing a systemic illness termed sarcoidosis. The
mechanisms involved in granuloma formation in the lung have not
been elucidated entirely. However, studies performed in animal
models of granuloma formation and in humans suggest important
roles for specific soluble mediators (eg, cytokines, chemokines)
produced by monocytic cells. If uncontrolled, granulomatous
inflammation leads to excessive tissue remodeling, causing
fibrosis and/or cavitation as seen in tuberculosis. This review
summarizes our current understanding of the factors involved in
granuloma formation in the lung with particular attention to their
role in sarcoidosis and tuberculosis.
Expression
profiling in granulomatous lung disease.Proc
Am Thorac Soc. 2007 Jan;4(1):101-7.
Granulomatous lung diseases, such as sarcoidosis, hypersensitivity
pneumonitis, Wegener's granulomatosis, and chronic beryllium
disease, along with granulomatous diseases of known infectious
etiologies, such as tuberculosis, are major causes of morbidity
and mortality throughout the world. Clinical manifestations of
these diseases are highly heterogeneous, and the determinants of
disease susceptibility and clinical course (e.g., resolution vs.
chronic, progressive fibrosis) are largely unknown. The underlying
pathogenic mechanisms of these diseases also remain poorly
understood. Within this context, these diseases have been
approached using genomic and proteomic technologies to allow us to
identify patterns of gene/protein expression that track with
clinical disease or to identify new pathways involved in disease
pathogenesis. The results from these initial studies highlight the
potential for these "-omics" approaches to reveal novel insights
into the pathogenesis of granulomatous lung disease and provide
new tools to improve diagnosis, clinical classification, course
prediction, and response to therapy. Realizing this potential will
require collaboration among multidisciplinary groups with
expertise in the respective technologies, bioinformatics, and
clinical medicine for these complex diseases.
Pulmonary
angiitis and granulomatosis revisited.Hum
Pathol. 1983 Oct;14(10):868-83.
Re-examination of the pathologic and clinical features of the
entities traditionally classified under the heading "pulmonary
angiitis and granulomatosis" indicates that there is little
advantage in retaining this artificial category and that these
entities should be considered variants of diseases to which they
are actually related. Wegener's granulomatosis and allergic
angiitis and granulomatosis appear to be examples of true systemic
vasculitides in which the lung is a predominant but not the only
or even the most important site of involvement. Wegener's
granulomatosis may manifest with involvement limited to lung, a
form that has been called limited Wegener's; however, many or most
such cases progress to classic disease involving kidney and often
upper respiratory tract. Similarly, Wegener's granulomatosis may
present with disease limited initially to the upper respiratory
tract (a form of midline granuloma); this process may also spread
to involve lung and kidney. It seems unlikely that limited
Wegener's is truly a separate disease category. Evaluation of the
pathologic and clinical features of necrotizing sarcoid
granulomatosis indicate that it very much resembles ordinary
sarcoid in most histologic features, in the nature of
extrapulmonary involvement, and in its clinical course and that it
probably corresponds to the clinical--radiographic entity of
nodular sarcoid. Lymphomatoid granulomatosis appears to have
little relationship to the other members of the angiitis and
granulomatosis group; its behavior and histologic features are
those of a lymphoproliferative disorder that in most cases is or
becomes histiocytic lymphoma. Some cases of so-called benign
lymphocytic angiitis also fall into this category; the remainder
appear to represent a variety of completely unrelated pathologic
processes. Last, bronchocentric granulomatosis is most commonly
one of the histologic manifestations of allergic bronchopulmonary
aspergillosis, although it is likely that other agents or
processes produce the same histologic pattern. Although the
presence of a common set of pathologic features makes the concept
of angiitis and granulomatosis attractive from a morphologic point
of view, there is minimal clinical similarity among them, and
these diseases appear to be totally separate entities.
Pulmonary angiitis and granulomatosis: a review.Can
Assoc Radiol J. 1989
Jun;40(3):127-34.
Vasculitis
is a clinical-pathological process characterized by inflammation
and necrosis of blood vessels. It has been effectively classified
by Fauci. Granulomatosis in the lung may be angiocentric or
bronchocentric in distribution. The angiocentric forms of
granulomatosis and vasculitis include Wegener's granulomatosis,
allergic angiitis and granulomatosis of Churg and Strauss,
lymphomatoid granulomatosis, and necrotizing sarcoid
granulomatosis. Wegener's granulomatosis is a well-defined
syndrome characterized by necrotizing granulomatous vasculitis of
the upper and lower respiratory tracts, segmental necrotizing
glomerulonephritis, and systemic small vessel vasculitis. Allergic
angiitis and granulomatosis is a less common multisystem
vasculitis with many features similar to polyarteritis nodosa.
Lymphomatoid granulomatosis is an angiocentric and
angiodestructive lymphoreticular proliferative and granulomatous
disease involving predominantly the lungs and resembling lymphoma.
Necrotizing sarcoid granulomatosis is probably a variant of
sarcoidosis in which an angiitis is a prominent feature. Because
the radiology of these diseases can be similar, their important
differences are highlighted. The appearance of multiple nodules,
often with cavities, and pleural-based consolidations resembling
pulmonary infarcts should suggest pulmonary angiitis and
granulomatosis, especially if improvement occurs in one area while
disease is progressing elsewhere. Bronchocentric granulomatosis is
not a primary vasculitis but is discussed because of its
similarity to the other diseases.
Pulmonary
hyalinizing granuloma. A limited form of Wegener's granulomatosis?Ann
Ital Med Int. 1998
Jul-Sep;13(3):176-9.
Pulmonary
hyalinizing granuloma is an uncommon disease that consists of
slowly enlarging nodules in the pulmonary parenchyma. It occurs
rarely: in fact, fewer than 70 case reports have been published in
the past 20 years. It is important however in the differential
diagnosis of lung diseases manifesting multiple pulmonary nodules.
The etiology and pathogenesis of this disorder are unknown.
Evidence suggests that the nodules could be the result of a
chronic exaggerated immune response to infectious agents or to any
other process in which antigen-antibody complexes are involved.
More than 50% of the patients reported have evidence of autoimmune
phenomena, e.g. positive antinuclear antibodies, a positive
rheumatoid factor, or circulating immune complexes. The present
report describes, for the first time, a case of pulmonary
hyalinizing granuloma in which the patient had antineutrophil
cytoplasmic autoantibodies with a granular cytoplasmatic pattern
with typical central accentuation of fluorescence intensity and
negative nuclei. The presence of antineutrophil cytoplasmic
autoantibodies suggests that pulmonary hyalinizing granuloma could
be regarded as a localized, non-evolving, form of Wegener's
granulomatosis or a purely granulomatous Wegener's granulomatosis.
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