Amyloidosis of the Lung
Andras Khoor, MD, PhD; Thomas V. Colby, MD
 Context.—Amyloidosis is a heterogeneous group of
diseases characterized by the deposition of congophilic
amyloid fibrils in the extracellular matrix of tissues and
organs. To date, 31 fibril proteins have been identified in
humans, and it is now recommended that amyloidoses be
named after these fibril proteins. Based on this classifica-
tion scheme, the most common forms of amyloidosis
include systemic AL (formerly primary), systemic AA
(formerly secondary), systemic wild-type ATTR (formerly
age-related or senile systemic), and systemic hereditary
ATTR amyloidosis (formerly familial amyloid polyneurop-
athy). Three different clinicopathologic forms of amyloid-
osis can be seen in the lungs: diffuse alveolar-septal
amyloidosis, nodular pulmonary amyloidosis, and tracheo-
bronchial amyloidosis.
Objective.—To clarify the relationship between the fibril
protein–based amyloidosis classification system and the
clinicopathologic forms of pulmonary amyloidosis and to
T he term amyloid (starchlike) was introduced into the
medical literature by Rudolph Virchow in 1854, when
he made the observation that corpora amylacea in the
brain stained similarly to starch, that is, stained pale blue
after treatment with iodine, and violet upon the subse-
quent addition of sulfuric acid.1,2 The name amyloid now
encompasses a wide variety of fibrillary proteins that
exhibit similar tinctorial, ultrastructural, and x-ray diffrac-
tion properties.
In hematoxylin-eosin–stained sections, amyloid appears
as homogeneous eosinophilic material. Congo red–stained
deposits are orange-red with bright field microscopy and
display apple-green birefringence under polarized light
(Figure 1, A and B). Ideally, Congo red staining is performed
on 10-lm sections, and the apple-green birefringence is
often best appreciated with the ambient room lights off. This
apple-green birefringence under polarized light is consid-
ered the gold standard for identifying a substance as
Accepted for publication June 2, 2016.
From the Department of Laboratory Medicine and Pathology,
Mayo Clinic Florida, Jacksonville (Dr Khoor); and the Department of
Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale
(Dr Colby).
The authors have no relevant financial interest in the products or
companies described in this article.
Portions based on a presentation given at the 2016 Mayo Clinic
Pathology Update: A Tribute to the Career of Thomas V. Colby, MD;
February 4, 2016; Phoenix, Arizona.
Reprints: Andras Khoor, MD, PhD, Department of Laboratory
Medicine and Pathology, Mayo Clinic, 4500 San Pablo Rd S,
Jacksonville, FL 32224 (email: khoor.andras@mayo.edu).
Arch Pathol Lab Med—Vol 141, February 2017
provide a useful guide for diagnosing these entities for the
practicing pathologist.
Data Sources.—This is a narrative review based on
PubMed searches and the authors’ own experiences.
Conclusions.—Diffuse alveolar-septal amyloidosis is
usually caused by systemic AL amyloidosis, whereas
nodular pulmonary amyloidosis and tracheobronchial
amyloidosis usually represent localized AL amyloidosis.
However, these generalized scenarios cannot always be
applied to individual cases. Because the treatment options
for amyloidosis are dependent on the fibril protein–based
classifications and whether the process is systemic or
localized, the workup of new clinically relevant cases
should include amyloid subtyping (preferably with mass
spectrometry–based proteomic analysis) and further clin-
ical investigation.
(Arch Pathol Lab Med. 2017;141:247–254; doi: 10.5858/
arpa.2016-0102-RA)
amyloid in histologic sections. In addition to Congo red,
amyloid can also be stained by thioflavin T and metachro-
matic dyes, such as crystal violet. Electron microscopy scans
of amyloid typically reveal haphazardly arranged non-
branching fibrils that measure 8 to 10 nm in diameter2
(Figure 2), and x-ray diffraction demonstrates a character-
istic cross-b pattern.3
Approximately 95% of amyloid is composed of fibril
proteins, and the remaining 5% consists of serum amyloid P
component and other glycoproteins. The insoluble fibril
proteins originate from improper folding of soluble precur-
sors because some proteins with a normal amino acid
sequence are prone to misfolding when they are produced
in an excessive amount (eg, immunoglobulin light chains,
serum amyloid A, and wild-type transthyretin). Misfolding
may also result from an abnormal amino acid sequence (eg,
transthyretin variants). To date, 31 human fibril proteins
have met the criteria from the International Society of
Amyloidosis (ISA) Nomenclature Committee.4 These criteria
include unambiguous characterization of the amyloid fibril
protein by protein sequence analysis and publication of the
findings in a peer-reviewed journal. The fibril proteins most
commonly encountered by pathologists include AL, AA,
and ATTR. Precursor proteins for AL, AA, and ATTR fibril
proteins are immunoglobulin light chains, (apo) serum
amyloid A, and transthyretin (wild type and variants),
respectively.
Major amyloid subtypes can be identified by immuno-
histochemistry. Antibodies are readily available for j and k
light chains, serum amyloid A, and transthyretin (preal-
bumin). Immunohistochemistry can be performed on
Amyloidosis of the Lung—Khoor & Colby 247

Figure 1. Congo red–stained amyloid deposits are orange-red with
bright field microscopy (A) and display apple-green birefringence under
polarized light (B) (original magnification 3200 [A and B]).
Figure 2. Electron micrograph of amyloid, showing haphazardly
arranged nonbranching fibrils that measure 8 to 10 nm in diameter
(original magnification 349 000).
frozen or paraffin sections with immunofluorescence or
immunoperoxidase techniques, respectively. However, the
classification of amyloid by immunohistochemistry is often
challenging owing to abundant background staining. Laser
248 Arch Pathol Lab Med—Vol 141, February 2017
microdissection followed by mass spectrometry–based
proteomic analysis can be performed on formalin-fixed,
paraffin-embedded tissue.5 This technique offers high
sensitivity and specificity and is now considered the
preferred method for amyloid subtyping.5
The deposition of amyloid in the extracellular matrix of
various tissues and organs is called amyloidosis. It is a
heterogeneous group of diseases caused by a variety of fibril
proteins deposited under a variety of conditions. Amyloid-
osis can be acquired or hereditary, systemic or localized.
Because treatment options and the prognosis of various
forms of amyloidosis can differ, precise identification of the
disease process is pivotal. The ISA recommends that names
of various forms of amyloidosis follow the names of fibril
proteins.4 Whether the disease is systemic or localized
should also be noted. The use of historical names such as
primary and secondary amyloidosis is now discouraged and
should be avoided.
The most common forms of amyloidosis include systemic
AL amyloidosis (formerly primary amyloidosis), systemic
AA amyloidosis (formerly secondary amyloidosis), systemic
wild-type ATTR amyloidosis (formerly age-related or senile
systemic amyloidosis), systemic hereditary ATTR amyloid-
osis (formerly familial amyloid polyneuropathy), and local-
ized AL amyloidosis (Table 1).4 Involvement of the lungs is
relatively common but rarely symptomatic. From the
pathologists’ perspective, amyloidosis can appear in the
lungs in 3 distinct forms: diffuse alveolar-septal amyloidosis,
nodular pulmonary amyloidosis, and tracheobronchial
amyloidosis.
DIFFUSE ALVEOLAR-SEPTAL AMYLOIDOSIS
Definition
Diffuse alveolar-septal amyloidosis, also known as diffuse
parenchymal amyloidosis, is characterized by the presence
of amyloid deposits in the alveolar septa and vessel walls. As
a rule, it is a manifestation of systemic amyloidosis, but
unusual cases of diffuse alveolar-septal amyloidosis with no
evidence of a systemic disease have been described.6–8 The
most common association is systemic AL amyloidosis,9,10
but cases of diffuse alveolar-septal amyloidosis that are
caused by systemic AA, systemic wild-type ATTR, and
systemic hereditary ATTR amyloidosis have also been
reported (Table 2).9,11,12
Clinical Features
Diffuse alveolar-septal amyloidosis is rarely symptomat-
ic.10,13 The patient’s symptoms are usually related to the
deposition of amyloid in other organs. The treatment
options and prognosis are dependent on the amyloid
subtype.
Systemic AL amyloidosis (formerly primary amyloidosis) is
a monoclonal plasma cell proliferative disorder in which
monoclonal immunoglobulin light chains are deposited in
tissues. It may be preceded by monoclonal gammopathy of
undetermined significance and may occur in association
with other plasma cell dyscrasias, such as multiple
myeloma and Waldenström macroglobulinemia.14 Elderly
men are more commonly affected than other demographic
groups. 15 Affected patients present with nonspecific
symptoms, such as fatigue and unintentional weight loss.
Clinical signs depend on the organs involved and may
include nephrotic syndrome, restrictive cardiomyopathy,
peripheral neuropathy, hepatomegaly with elevated liver
Amyloidosis of the Lung—Khoor & Colby
 enzymes, macroglossia, purpura, and an unexplained
bleeding diathesis. The International Myeloma Working

Chemotherapy, autologous
Group requires the following criteria for a diagnosis of

Treatment of underlying
systemic AL amyloidosis: (1) the presence of a systemic

stem cell transplant

Heart failure therapy

Localized treatment
amyloid-related syndrome; (2) proof of amyloid deposition
Treatment
in any tissue by a Congo red stain; (3) proof that the

Liver transplant
deposits are composed of immunoglobulin light chains;

condition
and (4) evidence of a monoclonal plasma cell proliferative
disorder.16 Systemic AL amyloidosis is usually treated with
chemotherapy followed by autologous stem cell trans-
plant.17
Systemic AA amyloidosis (formerly secondary amyloid-
Heart failure or peripheral
Symptoms and Signs

osis) is due to tissue deposition of serum amyloid A,

Nephrotic syndrome

which is an acute phase reactant produced by the liver. It

Depend on location
Depend on organs

is usually ‘‘secondary’’ to a chronic inflammatory condi-

tion, such as rheumatoid arthritis, juvenile chronic
neuropathy
Heart failure

polyarthritis, ankylosing spondylitis, inflammatory bowel

involved

disease, familial Mediterranean fever, or a chronic

infection.18–22 It can affect a variety of organs, including
the kidneys. The development of nephrotic syndrome in a
patient with a chronic inflammatory condition is often
All organs (except central

Heart, peripheral nervous

lungs, urinary bladder

suggestive of AA amyloidosis, but biopsy confirmation is

Tracheobronchial tree,

required for the diagnosis. AA amyloidosis is preferably

Target Organs

nervous system)

managed by treating the underlying disease. Colchicine

has been used widely for both prophylactic and thera-
Common Forms of Amyloidosis

peutic purposes.23 If left untreated, AA amyloidosis has

system

significant mortality due to end-stage renal disease,

Kidneys

infection, heart failure, bowel perforation, or gastrointes-

Heart

tinal bleeding.19,21,24 However, successful treatment of the

underlying condition can lead to stabilization or improve-
Underlying Condition

Chronic inflammatory

ment of renal function.21

Plasma cell dyscrasia

transthyretin gene

Systemic wild-type ATTR amyloidosis (formerly age-

MALT lymphoma

related or senile systemic amyloidosis) refers to the

Mutations in

deposition of unmutated transthyretin in tissues, often in

condition

the myocardium, in elderly individuals. 25,26 Affected

patients present with heart failure or arrhythmia. Signif-
Age

icant renal involvement is rare. Recognition is important

because survival is better than that associated with AL
Table 1.

Transthyretin, wild type

(Apo) serum amyloid A

amyloidosis, and chemotherapy or autologous stem cell

Transthyretin, variants
Immunoglobulin light

Immunoglobulin light
Precursor Protein

transplant is contraindicated.
Systemic hereditary ATTR amyloidosis (formerly familial
amyloid polyneuropathy) is caused by mutations in the
transthyretin gene. The most common mutation in the
chain

chain

United States27 and the United Kingdom is Thr60Ala

(T60A).28 Clinically, there may be considerable overlap
between wild-type ATTR amyloidosis and hereditary ATTR
Abbreviation: MALT, mucosa-associated lymphoid tissue.

amyloidosis. Because a family history may not be apparent,

systemic amyloidosis
Secondary amyloidosis
Previous Terminology

DNA sequencing may be necessary to distinguish these 2

Age-related or senile
Primary amyloidosis

causes of restrictive cardiomyopathy in elderly individu-

polyneuropathy
Familial amyloid

als.29 Because transthyretin is made by the liver, liver

transplant with a donor liver that produces unmutated
transthyretin may lead to regression of hereditary ATTR
amyloidosis.29 Chemotherapy and autologous stem cell
transplant have no role in the treatment of hereditary
amyloidosis.
Localized AL amyloidosis
Systemic hereditary ATTR
Systemic AA amyloidosis

Systemic wild-type ATTR

Systemic AL amyloidosis
Current Terminology

Pathology
With rare exceptions, diffuse alveolar-septal amyloidosis
is a manifestation of systemic AL, AA, wild-type ATTR, or
amyloidosis

amyloidosis

hereditary ATTR amyloidosis. Because pulmonary impair-

ment rarely dominates the clinical picture, pathologists
most often encounter diffuse alveolar-septal amyloidosis
as a postmortem finding. On the autopsy table, the lungs
are rubbery, and their cut sections have a uniform
spongelike appearance. Typically, all lobes are involved.
Arch Pathol Lab Med—Vol 141, February 2017 Amyloidosis of the Lung—Khoor & Colby 249
 Table 2. The Etiology of Pulmonary Amyloidosis
Subtype of Amyloidosis Source, y
Diffuse alveolar-septal amyloidosis
Typical scenario
- Systemic AL Cordier,10 2005; Utz et al,9 1996
Case reports
- Systemic AA Utz et al,9 1996
- Systemic wild-type ATTR Utz et al,9 1996
- Systemic hereditary ATTR Utz et al,9 1996; Authier et al,11 1999; Ueda et al12 2006
- Localized AL BoydKing et al,7 2009; Hui et al,6 1986; Rajagopala et al,8 2010
Nodular pulmonary amyloidosis
Typical scenario
- Localized AL or AL/AH Grogg et al,33 2013; Kaplan et al,34 2005
Case reports
- Systemic AL Ikeda et al,35 1999; Okuda et al,36 2004
- Localized AA Beer and Edwards,37 1993; Calatayud et al,38 2007
- Localized wild-type ATTR Roden et al,40 2010
- Localized Ab2M/AL Yang et al,41 2009
Tracheobronchial amyloidosis
Typical scenario
- Localized AL Borie et al,62 2012; Capizzi et al,58 2000; da Costa and Corrin,54 1985; Hui et al,6 1986;
O’Regan et al,55 2000; Utz et al,9 1996
Case reports
- Systemic AL Capizzi et al,58 2000
- Systemic AA Celli et al,59 1978; Kirbas et al,60 2009
Abbreviations: AL/AH, mixed immunoglobulin light chain/heavy chain; Ab2M/AL, mixed b2-microglobulin/immunoglobulin light chain.

Figure 3. Diffuse alveolar-septal amyloidosis. Amyloid deposits can be seen in the alveolar septa, particularly around arterioles and venules
(hematoxylin-eosin, original magnifications 380 [A] and 3150 [B]).
Figure 4. Nonspecific interstitial pneumonia, fibrosing pattern. A, Low-magnification view shows uniform thickening of alveolar septa. B, At higher
magnification, the alveolar septal thickening is due to collagen deposition (hematoxylin-eosin, original magnifications 340 [A] and 3200 [B]).

250 Arch Pathol Lab Med—Vol 141, February 2017 Amyloidosis of the Lung—Khoor & Colby

Figure 5. Gross photograph of nodular pulmonary amyloidosis,
showing an irregular, waxy gray-tan cut surface.
Figure 6. Nodular pulmonary amyloidosis. A, At low magnification,
the nodule is composed of homogeneous, densely eosinophilic
material. B, Higher magnification reveals a multinucleated giant cell
(arrow) and ossification (hematoxylin-eosin, original magnifications 36
[A] and 3140 [B]).
The visceral pleura may also be affected; pleural involve-
ment correlates with pleural effusion. Histologically, at
low magnification, the pulmonary architecture appears to
be well preserved. However, at higher magnification, the
alveolar septa are thickened by glassy eosinophilic
Arch Pathol Lab Med—Vol 141, February 2017
material (Figure 3, A and B). The vessel walls are often
involved, and small nodules may be formed. Amyloid
material may also be seen in the visceral pleura. The
lesions are typically hypocellular, but scant plasma cells
may be present. Giant cells are not usually seen with
diffuse alveolar-septal amyloidosis.
Congophilia with apple-green birefringence under polar-
ized light is diagnostic of amyloidosis. As mentioned above,
various forms of systemic amyloidosis are treated differently.
Therefore, if diffuse alveolar-septal amyloidosis is diagnosed
in a biopsy specimen, amyloid subtyping is pivotal. It can be
done by immunohistochemistry, but mass spectrometry–
based proteomic analysis has a higher sensitivity and
specificity and is considered the preferred method for
amyloid subtyping.5
In hematoxylin-eosin–stained sections, amyloid and
collagen are somewhat similar in appearance. As a result,
diffuse alveolar-septal amyloidosis is sometimes confused
with a fibrosing interstitial pneumonia, such as usual
interstitial pneumonia or fibrosing nonspecific interstitial
pneumonia (Figure 4, A and B). The presence of perivascular
glassy eosinophilic deposits may be a tip-off, and a Congo
red stain can be used to confirm the diagnosis. Pathologists
should have a low threshold for ordering a Congo red stain,
if amyloidosis is suspected.
Similar to systemic AL amyloidosis, light chain deposition
disease is a monoclonal plasma cell proliferative disorder.
Lung involvement by light chain deposition disease may
mimic either diffuse alveolar-septal amyloidosis or nodular
pulmonary amyloidosis (see below).30 The diffuse form is
histologically indistinguishable from diffuse alveolar-septal
amyloidosis. However, nonamyloid light-chain deposits are
Congo red negative. Furthermore, electron microscopy
reveals a granular material instead of the typical fibrils seen
in amyloidosis. Light chain deposition disease produces j
light chains as a rule, whereas k light chains are more
common in systemic AL amyloidosis and diffuse alveolar-
septal amyloidosis.31,32
NODULAR PULMONARY AMYLOIDOSIS
Definition
Nodular pulmonary amyloidosis, also known as nodular
parenchymal amyloidosis or nodular amyloidoma, is defined
as 1 or more tumefactive amyloid deposits involving the
lungs. It usually represents localized AL or AL/AH (mixed
immunoglobulin light chain/heavy chain) amyloidosis,33,34
but rare cases of systemic AL, localized AA, localized wild-
type ATTR, and localized Ab2M/AL (mixed b2-microglobu-
lin/immunoglobulin light chain) amyloidosis have been
reported (Table 2).35–41 Of note, localized AL amyloidosis is
not unique to the lungs and the tracheobronchial tree (see
below). It can also occur at other sites including the larynx,42
urinary bladder,43 and colon.44
In the past, nodular pulmonary amyloidosis and primary
pulmonary lymphoma with amyloid production were
thought to be 2 fundamentally different processes.45,46
However, many experts now believe that most cases of
nodular pulmonary amyloidosis are the result of an
underlying lymphoproliferative disorder in the spectrum of
extranodal marginal zone lymphoma of mucosa-associated
lymphoid tissue (MALT lymphoma).33 The underlying
lymphoproliferative disorder might be subtle, but sensitive
methods reveal a clonal B-cell population in most cas-
es.33,47,48
Amyloidosis of the Lung—Khoor & Colby 251
Figure 7. Pulmonary hyalinizing granuloma. A, Low-magnification view shows a well-demarcated, eosinophilic nodule. B, Higher magnification
reveals thick collagen bundles arranged in lamellae (hematoxylin-eosin, original magnifications 320 [A] and 3270 [B]).
Figure 8. Light chain deposition disease is histologically indistinguishable from nodular pulmonary amyloidosis; however, Congo red staining is
negative (not shown) (hematoxylin-eosin, original magnifications 320 [A] and 3400 [B]).

Clinical Features under polarized light is diagnostic of amyloidosis. Addi-

Similar to other forms of amyloidosis, nodular pulmo-
nary amyloidosis is also rare. The mean age of patients is
67 years, and the male to female ratio is 3:2.9,49 The
nodules are usually solitary and asymptomatic and are
discovered incidentally during chest imaging studies
performed for unrelated reasons. Unusual cystic radiologic
features have been described.50 Because most cases of
nodular pulmonary amyloidosis are localized, conservative
excision is usually curative, and the long-term prognosis
is excellent. Nevertheless, it is important to confirm the
absence of systemic amyloidosis, which requires addi-
tional treatment.
Pathology
Gross examination of the lungs reveals 1 or rarely more
nodules, which typically measure 0.4 to 5 cm in greatest
dimension.9 However, larger masses measuring up to 15 cm
in greatest dimension have been reported.6 The cut surface
of the lesions is waxy, gray-tan (Figure 5). Histologically, the
nodules are well circumscribed and are composed of
homogeneous, densely eosinophilic material (Figure 6, A).
Small aggregates of lymphocytes and plasma cells are
usually found within or adjacent to the nodules. Foreign
body giant cells, calcifications, and bony or cartilaginous
areas may also be seen (Figure 6, B).
If amyloid is suspected, a Congo red stain should be
performed. Congophilia with apple-green birefringence
252 Arch Pathol Lab Med—Vol 141, February 2017
tional studies should include amyloid subtyping (preferably
with mass spectrometry–based proteomic analysis), an
attempt to reveal an underlying localized lymphoprolifer-
ative disorder, and, although it is exceptionally rare in this
context, exclusion of a plasma cell dyscrasia. Amyloid
subtyping usually reveals monoclonal immunoglobulin
light chains. Interestingly, the light chains in nodular
pulmonary amyloidosis are more frequently of j than of k
type, with a ratio of 3:1, in contrast to the k predominance
noted in most cases of systemic AL amyloidosis.33 In rare
cases of nodular pulmonary amyloidosis, serum amyloid A
or transthyretin may be detected.8,37,38,40 The clonality of
the lymphoplasmacytic component can be evaluated by
immunohistochemistry for j and k light chains or
immunoglobulin gene rearrangement analysis. Exclusion
of a plasma cell dyscrasia requires further clinical consid-
eration and laboratory testing.
Differential diagnoses of nodular pulmonary amyloidosis
include pulmonary hyalinizing granuloma and amyloid-
like nodules, particularly light chain deposition disease.51
Similar to nodular pulmonary amyloidosis, pulmonary
hyalinizing granuloma often presents as incidental solitary
or multiple nodules on chest imaging studies performed for
unrelated reasons. The histologic appearance of the 2
entities, however, is somewhat different. Unlike amyloid,
which is homogeneous in appearance, pulmonary hyali-
nizing granuloma is composed of thick collagen bundles
arranged in lamellae (Figure 7, A and B). Bony and
Amyloidosis of the Lung—Khoor & Colby
cartilaginous areas are not seen in pulmonary hyalinizing
granuloma. Most importantly, Congo red staining is
negative.
Amyloid-like nodules are histologically indistinguishable
from nodular pulmonary amyloidosis, but Congo red
negative (Figure 8, A and B). They are usually composed of
nonamyloid light chains (typically j), which means that the
light chain fragments do not form fibrils and electron
microscopy shows a granular material.52 Although a localized
form has been reported,51,53 nonamyloid light-chain deposi-
tion in the lungs is usually associated with systemic light
chain deposition disease.30,31 Since most patients with light
chain deposition disease show evidence of renal involvement
and an underlying monoclonal plasma cell proliferative
disorder, the presence of appropriate clinical features may
also be helpful in separating light chain deposition disease
from nodular pulmonary amyloidosis.

TRACHEOBRONCHIAL AMYLOIDOSIS
Definition
Tracheobronchial amyloidosis is characterized by amyloid
deposition in various segments of the tracheobronchial tree.
Most cases represent localized AL amyloidosis and are
restricted to the tracheobronchial tree (Table 2).6,9,54,55 The
alveolated parenchyma is typically not involved, but
colocalization of laryngeal and tracheal amyloidosis has
been described.56,57 Furthermore, rare cases of tracheobron-
chial amyloidosis caused by systemic AL58 and systemic
AA59,60 amyloidosis have been reported.
Clinical Features
Tracheobronchial amyloidosis is the least common form
of pulmonary amyloidosis; approximately 100 cases have
been reported. The mean age of patients is somewhere
between 48 and 57 years.6,55,58 There is no sex predilection.
In individual cases, various segments of the tracheobron-
chial tree are involved to various extents. Three patterns of
involvement have been described: proximal, mid, and distal
airway disease.55 Patients usually present with dyspnea,
cough, hemoptysis, or hoarseness. Bronchoscopy with
transbronchial biopsy is most useful for establishing the
diagnosis of tracheobronchial amyloidosis, whereas com-
puted tomography is very helpful for determining the extent
of the disease.55 On pulmonary function tests, patients with
proximal airway disease have decreased airflows, whereas
patients with distal airway disease have normal airflows.
Proximal and severe mid airway disease can lead to airway
compromise, which is usually treated with laser or forceps
debridement, or external beam radiation therapy.55,61
Recurrence is common after laser or forceps debridement, Figure 9. Bronchoscopic image of tracheobronchial amyloidosis,
and approximately 30% of these patients eventually die of showing submucosal deposits.
the disease.55 However, external beam radiation therapy Figure 10. Tracheobronchial amyloidosis. A, At low magnification,
may offer better outcomes.61 amyloid deposits surround seromucous glands and cartilage plates. B,
Higher magnification shows eosinophilic deposits, a lymphoplasmacyt-
Pathology ic infiltrate, and ossification (hematoxylin-eosin, original magnifications
In tracheobronchial amyloidosis, the walls of the affected 310 [A] and 3180 [B]).
airways are thickened, and there is luminal narrowing. If
grossly visible, the deposits are located in the submucosa
(Figure 9). Histologically, the deposits are composed of Congophilia with apple-green birefringence under polar-
homogeneous eosinophilic material and surround seromu- ized light is diagnostic of amyloidosis. If amyloid subtyping
cous glands and cartilage plates (Figure 10, A). Small is performed, it should reveal monoclonal immunoglobulin
submucosal vessels are involved in most cases. Plasma cells, light chains. Lambda light chains are more commonly
foreign body–type giant cells, calcifications, and ossification detected than j light chains.56 Polymerase chain reaction
are common findings (Figure 10, B).6 may detect a localized clonal expansion of B cells.62
Arch Pathol Lab Med—Vol 141, February 2017 Amyloidosis of the Lung—Khoor & Colby 253
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Amyloidosis of the Lung—Khoor & Colby