(Chest. 2000;117:80S-89S.)
© 2000
American College of Chest Physicians
Diagnosis of Lung Cancer*
Pathology of Invasive and Preinvasive Neoplasia
Wilbur A. Franklin, MD
*
From the University of Colorado Cancer Center and SPORE in Lung Cancer, Denver, CO.
Correspondence to: Wilbur A. Franklin, MD, University of Colorado Health Sciences Center, Department of Pathology, Box B216, 4200 East Ninth Ave, Room 2511, Denver, CO 80262; e-mail: wilbur.franklin{at}uchsc.edu
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Abstract
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The histopathologic appearance of lung carcinoma remains an
important guide to prognosis and treatment. The newly revised World
Health Organization classification retains the broadest pathologic
categories of the older classification but includes several revisions,
including the elimination of the small cell, intermediate cell type
category; the addition of large cell neuroendocrine and spindle/giant
cell categories; and an extended consideration of preneoplastic
lesions. The histopathologic classification of lung cancer is expected
to continue to change as clinical practice and biological understanding
of these tumors change. The application of immunohistochemical testing
to histologic material not only provides new assistance with
conventional histologic classification, but also permits new ways to
subclassify tumors, the full clinical significance of which is yet to
be realized. The significance of expression of neuroendocrine markers,
histologic grading of response to chemotherapy, and delineation of
morphologic changes preceding the occurrence of invasive carcinoma are
all areas where understanding microscopic cellular changes in the
airways will be critical for clinical advance.
Key Words: histopathology • lung cancer • neoplastic • neuroendocrine tumors • non-small cell carcinoma • pathology • small cell carcinoma • squamous cell tumors
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Histopathology of Invasive Lung Neoplasia: the World Health
Organization Classification
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The
classification of lung cancer has long been rooted in the microscopic
appearances of tumor sections stained with hematoxylin and eosin. The
most widely accepted lung tumor classification schema is that of the
World Health Organization (WHO). This classification system is the
result of years of collaborative effort by a panel of pathologists
internationally recognized for their lung cancer expertise. The
classification is periodically updated, and the most recent update was
published in 1999.1
The aim of this panel has been to
define criteria for diagnostic categories that reflect the biology of
lung cancer and, at the same time, can be reproducibly applied in
virtually all anatomic pathology laboratories. The most recent previous
WHO classification was compiled in 1981; since that time, several new
pathologic entities have been described. The 1999 compilation,
therefore, represents an extensive revision of the older
classification. In the attached Appendix, diagnostic categories of the
new classification are shown. The broadest categories are retained from
the previous schema, and the revised classification will not require
major revisions of clinical intervention protocols. Thus, the most
clinically relevant categories of small cell and non-small cell
carcinoma are readily accommodated in the new classification. During
the past decade, a considerable body of information on
immunohistochemical staining properties, electron microscopic
appearances, and genetic abnormalities of lung cancer have been used to
refine and buttress classic microscopic classification. In most cases,
histologic features alone are sufficient to guide therapy, and
ancillary studies are primarily of academic interest. However, in a
minority of cases, tumors are insufficiently differentiated or biopsies
are too small to be classified by conventional histologic methods; in
these cases, additional information, particularly immunohistochemical
properties, may permit accurate histologic classification.
The Diagnostic Algorithm
Distinctions among the various diagnostic groups continue
to be made primarily on the basis of histologic appearances. Table 1 indicates histologic criteria distinguishing among major diagnostic
categories. In most cases, these criteria can be applied readily and
rapidly to well-prepared histologic and cytologic material by
experienced pathologists. However, some tumors and tumor-like
conditions may not be instantly recognizable, and it may be helpful to
apply the attached or similar diagnostic algorithm. Diagnostic problems
may be encountered at any decision point in the algorithm. In
recalcitrant cases, it may be necessary to apply appropriate
immunohistochemical tests. The expected results for each diagnostic
category are shown in Figure 1
. \
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Neoplastic vs Nonneoplastic Conditions
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Distinction
between reactive and neoplastic processes is usually straightforward,
but diagnostic difficulties may arise in the case of (1) inadequate or
poorly prepared histologic material to evaluate, or (2) the presence of
cytologic atypia in epithelium stimulated by inflammation, viral
infection, radiation, or chemotherapy. Immunohistochemical stains are
usually of no help in this circumstance. Diagnostic distinction between
atypical reactive epithelium and well-differentiated carcinoma,
especially adenocarcinoma, must ultimately rest on the subtle
morphologic clues, such as degree of nuclear atypia, numbers of
atypical cells, clustering pattern of suspicious cells, and extent of
inflammatory reaction in relation to the amount and degree of
epithelial atypia (Fig 2) . \
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Figure 2.. A cluster of large reactive epithelial cells
(top) from a patient with lung abscess. These cells are
distinguished from carcinoma cells (bottom) by their
abundant cytoplasm, their low nuclear/cytoplasmic ratio, the small
number of cells in clusters, and the prominent inflammatory
background.
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Epithelial vs Nonepithelial Tumors: On occasion, it
may be difficult to distinguish epithelial cells or epithelial tumor
cells from poorly differentiated lymphoid or stromal proliferations.
This may be especially true in large cell lymphoma, which, in the
chest, may be sclerotic and form cell clusters reminiscent of
carcinoma. In this case, differential staining for cytokeratin and
leukocyte antigens may be the only way to provide a definitive answer.
In situ vs Invasive Tumors: With increasing
reliance on smaller quantities of tissue, diagnostic decisions are made
on ever smaller amounts of tissue. This can be hazardous when
attempting to distinguish between invasive non-small cell carcinoma and
epithelial dysplasia or carcinoma in situ. At the
present time, the only certain way to diagnose invasive non-small cell
carcinoma is to specifically identify stromal invasion in tissue
sections. An extreme degree of cytologic atypia may suggest invasive
carcinoma and warrant the procurement of additional tissue to confirm
the diagnosis of invasive tumor.
Low-grade Endobronchial Lesions: Occasionally, lesions that
are primarily endobronchial may present diagnostic difficulties. These
are tumors of bronchial gland origin and carcinoid tumors. These tumors
are generally slow growing and exhibit different biological properties
than the more common small cell and non-small cell lung carcinomas.
Bronchial gland tumors usually have characteristic morphologic
appearances and are well described in several texts.2
3
4
Carcinoid tumors are morphologically distinct from the bronchial gland
tumors and are divided into typical and atypical types. Atypical
carcinoids are distinguished by the presence of necrosis and the 5 to
10 mitoses per 10 high-power fields. The 10-year survival rate among
patients with typical carcinoids is nearly 90%, while that in atypical
carcinoid is about 50%. This prognostic difference probably makes it
worthwhile to separate these tumors.
Small Cell vs Non-Small Cell Tumors: The two major
subgroupings of carcinoma, small cell and non-small cell carcinoma, can
be difficult to distinguish. It should be emphasized that
diagnosis of small cell carcinoma is made on the basis of nuclear
details, including high mitotic rate and inconspicuousness of nuclei
and finely granular ("salt and pepper") nuclei, as well as on
overall cell size. In general, the tumor cells of small cell carcinoma
are less than the diameter of three resting lymphocytes (< 21
µm). It is of interest that the revised
classification does not include the old categories of small cell
carcinoma, oat cell carcinoma and small cell carcinoma,
intermediate cell type. Rather, these are combined into the
single category of small cell carcinoma. Apparent cell
size and the nuclear details are dependent on the state of preservation
of the specimen, and severe crush artifact that frequently affects the
fragile tumor cells of small cell carcinoma may render diagnosis
difficult. We have found that, in most cases, small cell carcinoma
strongly expresses the neuroendocrine marker, neural cell adhesion
molecule (NCAM), and this can be demonstrated by a simple
immunohistochemical stain of a paraffin section using the monoclonal
antibody, 123c3; on the other hand, non-small cell carcinoma typically
expresses epidermal growth factor receptor (EGFR). These two markers
can sometimes be useful in confirming the diagnosis (Fig 3
and Table 2
). \
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Figure 3.. Immunoalkaline phosphatase stains of
(top, left) normal mucosa stained in
anti-EGFR. Staining is confined to the basilar layer of cells.
Non-small cell carcinoma (squamous cell carcinoma; top,
right) stained with anti-EGFR. Tumor cell membranes are
brightly labeled. Normal mucosa (bottom,
left) stained with NCAM. Only a single labeled cell is
present in this field. Small cell lung carcinoma
(bottom, right) stained with NCAM. Tumor
cells exhibit intense cell membrane staining.
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Differential Diagnosis of Non-Small Cell Carcinoma
Distinction among the different types of non-small cell carcinoma
can sometimes prove difficult. One ambiguity in older classification
systems is the question of when to diagnose tumors forming small
amounts of mucus, though the great majority of the tumor is squamous.
The new WHO classification establishes a 10% guideline; squamous
tumors with < 10% of cells containing mucin are to be classified as
squamous carcinoma.
The high degree of morphologic variability in non-small cell tumors is
taken into account by the incorporation of variants of the major tumor
types. An especially noteworthy variant of both squamous carcinoma and
large-cell carcinoma is termed basaloid carcinoma. This
tumor type is composed of relatively small cells with scant cytoplasm
and with nuclei that form parallel ("palisaded") rows at the edges
of tumor cell nests. Unique biological behavior is not documented for
this non-small cell variant, nor is it for any of the other variants of
non-small cell tumor types. However, in collecting data for therapeutic
trials, it would be prudent to take into account the wide range of
variants of non-small cell carcinoma so that new, prognostically
significant, tumor cell types are not overlooked.
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Immunohistochemistry
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As immunohistochemical methods have been increasingly applied to
lung carcinomas, characteristic immunophenotypic patterns have emerged
that correlate with conventional histologic classifications and, to a
large extent, with biological behavior. Three groups of tumors to which
immunohistochemical testing is especially relevant are discussed below.
Neuroendocrine Tumors
Neuroendocrine tumors and proliferations are regarded by
pathologists as a continuous spectrum of similar cell types of variable
clinical aggressiveness. These tumors include, in decreasing order of
aggressiveness, small cell lung carcinoma, large cell neuroendocrine
carcinoma, atypical carcinoid tumor, typical carcinoid tumor, tumorlet,
and diffuse idiopathic neuroendocrine cell hyperplasia. These tumors
share some morphologic features and express common neuroendocrine
markers, which can be demonstrated by immunohistochemical staining. A
list of immunostains that may be helpful in the differential diagnosis
is shown in Table 2
. Several notable immunophenotypic features of
various types of lung cancer are evident in this Table
. First, a large
number of tumors of varying biological potential express neuroendocrine
markers. There is some variation in the number of neuroendocrine
antibody markers with which the various tumors react. Some tumor types
react with virtually all neuroendocrine antibodies, while others, more
poorly differentiated tumors, react strongly with only a subset of
markers. There appears to be an inverse relationship between
chromogranin immunoreactivity and proliferation rate among
neuroendocrine tumors. Of particular note are large cell carcinomas.
These tumors may exhibit neuroendocrine histologic features such as
rosettes, scant cytoplasm, and characteristic finely granular nuclear
chromatin, or may be entirely undifferentiated, with expression of
neuroendocrine immunomarkers as the only manifestation of
neuroendocrine differentiation. Currently, no specific therapy is
available for large cell neuroendocrine carcinoma, and most protocols
consider them for therapeutic purposes to be non-small cell carcinoma.
Spindle Cell Tumors
Other tumor types for which immunohistochemistry may be
diagnostically helpful are the spindle cell tumors. The most common
primary spindle cell tumor arising in lung is epithelial and can
sometimes be distinguished from true sarcoma on the basis of positive
keratin stains. In the new WHO classification, spindle cell tumors of
epithelial derivation are assigned a new category, designated
carcinomas with pleomorphic, sarcomatoid or sarcomatous
elements, and include the subcategory, pleomorphic
carcinoma, which consists of tumors containing a malignant spindle
cell component constituting > 10% of the tumor and a component of
squamous carcinoma, adenocarcinoma, or large cell carcinoma. Pure
spindle cell neoplasms are classified as spindle cell carcinoma, and
are recognized as epithelial primarily on the basis of their keratin
expression. True stromal tumors such as desmoid tumors and
leiomyosarcoma may be distinguished from spindle cell carcinomas by
their morphologic properties, such as the loose, wavy collagen bundles
that characterize desmoid tumors, and by their immunophenotypic
properties, such as expression of desmin in leiomyosarcoma.
Mesothelioma
Finally, mesothelioma can sometimes present diagnostic problems
that demand the application of immunohistochemical testing.
Adenocarcinoma may resemble epithelioid mesothelioma. Distinction
between these tumors can usually be accomplished on the basis of
immunohistochemical reactivity. Adenocarcinomas are often
carcinoembryonic antigen (CEA)-positive, B72.3-positive, and
CD15(LeuM1)-positive, while mesothelioma is usually CEA-negative,
B72.3-negative, and CD15(LeuM1)-negative (Table 3
). In those unusual cases that cannot be resolved by conventional
histology and immunohistochemistry, electron microscopy may be helpful,
revealing the characteristic long filamentous cytoplasmic processes of
mesothelioma.
Evaluation of Treated Tumor
With increasing use of treatment protocols in which patients are
administered chemotherapy prior to surgery, pathologists are
increasingly being expected to evaluate the effects of chemotherapy on
treated tumors. Chemotherapy can affect the microscopic appearances of
lung carcinomas in a variety of ways. Tumors may largely disappear,
leaving behind only a fibrous scar or, more frequently, only a few
residual viable tumor cell nests in a fibrous scar. There may be a
granulomatous response to tumor cells and tumor cell breakdown products
such as keratin. Tumor cells may undergo coagulation necrosis, leaving
behind variably sized regions containing only the ghosts of tumor cells
(Fig 4)
.
Finally, chemotherapy may have no effect on the microscopic
appearance of the tumor. For purposes of documenting response to
chemotherapy, it is important to document the size of macroscopically
identifiable tumor and, on microscopic examination, to estimate the
proportion of the nodule that is viable tumor. If no tumor is evident
macroscopically, it is important to microscopically examine the entire
site formerly occupied by tumor, since small viable tumor nests may be
not be visible to the unaided eye. Results of assessment of the treated
tumor should be correlated with radiologic measurements of changes in
tumor size to arrive at an overall assessment of response to
chemotherapy. Such an approach, although not yet validated in clinical
trials, could potentially lead to a means of guiding further therapy.
Pathology of Preinvasive Lung Neoplasia
Carcinoma of the lung is the leading cause of cancer death in the
United States, and has been cited as a major reason for the failure of
the "war on cancer." In 1999, lung cancer was diagnosed in an
estimated 171,600 individuals, and an estimated 158,900 lung cancer
patients will die of their tumors.5
Attempts to reduce
mortality by large-scale sputum screening and chest radiograph have
proven expensive and ineffective. At the present time, sputum screening
is not recommended for lung cancer detection by the American Cancer
Society.
Field Carcinogenesis
New approaches to lung cancer detection are urgently needed, and
recent improvements in our understanding of lung carcinogenesis have
suggested a way forward. Increasing evidence suggests that lung cancer,
like other solid tumors, is the result of a multistep process, rather
than sudden transformation of previously normal epithelium. Evidence
for this hypothesis includes the frequent occurrence of multifocal
synchronous or metachronous tumors and dysplasias in the airways of
patients with lung cancer. Squamous metaplasia or dysplasia is
frequently found in association with invasive carcinomas of all
histologic types. Tissue sections of lung resection specimens harboring
invasive carcinoma and from lung specimens obtained at autopsy have
revealed squamous dysplasia distant from sites of invasive
tumor.6
Histologic abnormalities ranging from basal cell
hyperplasia to squamous carcinoma in situ also have been
observed in smokers without carcinoma.7
Finally,
multifocal synchronous carcinoma is observed in 7 to 12% of patients
with a prior invasive cancer.8
9
10
11
Thus, broad
areas of the tracheobronchial tree in patients at high risk are prone
to premalignant or multifocal malignant change, a phenomenon first
described in head and neck tumors and referred to as field
carcinogenesis.12
The squamous atypias and second
tumors accompanying or preceding invasive cancers represent varying
stages of neoplastic development in airways exposed to carcinogens
primarily present in tobacco smoke.
Field carcinogenesis has two alternate biological explanations. In one
scenario, high exposure of respiratory epithelium to multiple
carcinogens in tobacco smoke produces multiple different genetic
mutations at dispersed sites in the airways. This hypothesis is
supported by a study of multiple primary tumors, which indicates
separate genetic profiles,13
suggesting that separate
molecular pathways may lead to different mutational progression at
dispersed sites in the airways. An alternate explanation is that a
single, mutant, progenitor epithelial clone may expand over time to
populate widespread areas of the respiratory tract. Such a mechanism
would result in the occurrence of a common mutation at multiple sites.
Common allelic loss in multifocal bladder cancers is regarded as
evidence of origin of multiple bladder tumors from a single progenitor
cell.14
In the lung, identical abnormalities have been
found in lung carcinoma and adjacent nonmalignant epithelium. These
mutations have included loss of heterozygosity of chromosomes
3p15
16
17
18
and 9p,19
and point mutation in the
p53 tumor suppressor gene.16
17
20
21
22
Although the
evidence collected regarding the molecular mechanism of field
carcinogenesis appears contradictory thus far, a combination of these
mechanisms may, in fact, be responsible for lung carcinogenesis. In
such a scenario, cells harboring a single mutation would be at a
proliferative advantage over nonmutant bronchial cells. Expansion of
the mutant cell population would subject it to further mutations, the
cumulative effect of which would be transformation into invasive tumor.
Morphology of Squamous Preinvasive Lesions
Better understanding of lung carcinogenesis has stimulated renewed
interest in morphologic changes that occur in the bronchial epithelium
of smokers before the occurrence of invasive carcinoma. Earlier studies
have focused on advanced cytologic and histologic changes in the
airways, but it has been clear that a range of dysplasias occur in the
airways before or in association with invasive carcinoma. Recently, the
WHO/International Association for the Study of Lung Cancer panel has
begun to grapple with the reproducibility of the classification of
preinvasive bronchial lesions. The WHO histologic grading of squamous
preinvasive lesions, which was incorporated into the 1999 tumor
classification, is shown in Table 4
.
Not included in the classification and reported elsewhere 23
is a lesion referred to as angiogenic squamous
dysplasia. This lesion consists of microscopic projections into
the bronchial lumen, which are surfaced by squamous bronchial
epithelium exhibiting variable degrees of squamous dysplasia (Fig 5)
.
This lesion represents evidence of angiogenesis in the airways of
smokers before the occurrence of invasive carcinoma, and suggests that
intervention in angiogenesis mechanisms may be a means of inhibiting
the growth of preinvasive bronchial epithelium.
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Figure 5.. Histologic section of angiogenic squamous
dysplasia. A papillary projection with a vascular core surfaced by
mildly dysplastic squamous bronchial mucosa is the hallmark of this
lesion.
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Morphology of Nonsquamous Preinvasive Lesions
Since the previous WHO classification was published in 1981, two
nonsquamous lesions have been added to the WHO classification of
premalignant lesions, including atypical adenomatous hyperplasia and
diffuse idiopathic neuroendocrine cell hyperplasia. Both of these
lesions are rare. The former consists of a focal lesion < 5 mm in
diameter. Atypical adenomatous hyperplasia is composed of a peripheral
epithelial cell proliferation with minimal cytologic atypia or stromal
response and resembles bronchiolar carcinoma. The lesion has been seen
in lung specimens resected for lung cancer, but no prospective studies
of the prognostic significance of this lesion have been performed. The
second lesion, diffuse idiopathic neuroendocrine cell hyperplasia,
consists of a diffuse but patchy increase in the number of
well-differentiated neuroendocrine cells in the bronchioles. This
process may result in the formation of small carcinoid tumors, and for
this reason, it is considered "preinvasive." To date, small cell
carcinomas have not been found in association with the lesion.
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Conclusion
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Histopathologic diagnosis and subclassification will continue to
anchor lung cancer treatment for the foreseeable future. However, as
clinical practice changes, information required to diagnose and
effectively treat lung carcinomas will continue to change. For example,
the implementation of new presurgical chemotherapeutic protocols
generates specimens that permit histologic assessment of in
situ response to chemotherapy. Better understanding of preinvasive
histomorphologic changes and how these changes relate to molecular
abnormalities may permit earlier diagnosis and more effective
monitoring of chemoprevention trials. Finally, new technologies such as
rapidly developing microarray technology may embellish the information
that can be derived from the evaluation of surgical specimens, and may
enhance the diagnostic armamentarium of the clinical pathologist.
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Appendix 1
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WHO Histologic Classification of Lung and Pleural Tumors
(Reprinted with permission from Travis et
al.1
)
- Epithelial tumors
- 1.1 Benign
- 1.1.1 Papillomas
- 1.1.1.1 Squamous cell papilloma
- 1.1.1.1.1 Exophytic
- 1.1.1.1.2 Inverted
- 1.1.1.2 Glandular papilloma
- 1.1.1.3 Mixed squamous cell and glandular papilloma
- 1.1.2 Adenomas
- 1.1.2.1 Alveolar adenoma
- 1.1.2.2 Papillary adenoma
- 1.1.2.3 Adenomas of salivary gland type
- 1.1.2.3.1
Mucous gland adenoma
- 1.1.2.3.2
Pleomorphic adenoma
- 1.1.2.3.3
Others
- 1.1.2.4
Mucinous cystadenoma
- 1.1.2.5
Others
- 1.2
Preinvasive lesions
- 1.2.1
Squamous dysplasia/carcinoma in situ
- 1.2.2
Atypical adenomatous hyperplasia
- 1.2.3
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
- 1.3
Invasive malignant
- 1.3.1 Squamous cell carcinoma
- Variants:
- 1.3.1.1 Papillary
- 1.3.1.2 Clear cell
- 1.3.1.3 Small cell
- 1.3.1.4 Basaloid
- 1.3.2 Small cell carcinoma
- Variant:
- 1.3.2.1 Combined small cell carcinoma
- 1.3.3 Adenocarcinoma
- 1.3.3.1 Acinar
- 1.3.3.2 Papillary
- 1.3.3.3 Bronchioloalveolar carcinoma
- 1.3.3.3.1
Non-mucinous (Clara cell/type II pneumocyte type)
- 1.3.3.3.2
Mucinous (goblet cell type)
- 1.3.3.3.3
Mixed mucinous and nonmucinous (Clara cell/type II pneumocyte and
goblet cell type) or indeterminate
- 1.3.3.4
Solid adenocarcinoma with mucin formation
- 1.3.3.5 Mixed
- 1.3.3.6 Variants:
- 1.3.3.6.1
Well-differentiated fetal adenocarcinoma
- 1.3.3.6.2
Mucinous ("colloid")
- 1.3.3.6.3 Mucinous cystadenocarcinoma
- 1.3.3.6.4 Signet ring
- 1.3.3.6.5 Clear cell
- 1.3.4 Large cell carcinoma
- Variants:
- 1.3.4.1 Large cell neuroendocrine carcinoma
- 1.3.4.1.1
Combined large cell neuroendocrine carcinoma
- 1.3.4.2 Basaloid carcinoma
- 1.3.4.3 Lymphoepithelioma-like carcinoma
- 1.3.4.4 Clear cell carcinoma
- 1.3.4.5 Large cell carcinoma with rhabdoid phenotype
- 1.3.5 Adenosquamous carcinoma
- 1.3.6 Carcinomas with pleomorphic, sarcomatoid, or sarcomatous
elements
- 1.3.6.1 Carcinomas with spinle and/or giant cells
- 1.3.6.1.1 Pleomorphic carcinoma
- 1.3.6.1.2 Spinle cell carcinoma
- 1.3.6.1.3 Giant cell carcinoma
- 1.3.6.2 Carcinosarcoma
- 1.3.6.3 Blastoma (pulmonary blastoma)
- 1.3.6.4 Others
- 1.3.7 Carcinoid tumor
- 1.3.7.1 Typical carcinoid
- 1.3.7.2 Atypical carcinoid
- 1.3.8 Carcinomas of salivary gland type
- 1.3.8.1 Mucoepidermoid carcinoma
- 1.3.8.2 Adenoid cystic carcinoma
- 1.3.8.3 Others
- 1.3.9 Unclassified carcinoma
- Soft tissue tumors
- 2.1 Localized fibrous tumor
- 2.2 Epithelioid hemangioendothelomia
- 2.3 Pleuroplmonary blastoma
- 2.4 Chondroma
- 2.5 Calcifying fibrous pseudotumor of the pleura
- 2.6 Congenital periobronchial myofibroblastic tumor
- 2.7 Diffuse pulmonary lymphangiomatosis
- 2.8 Desmoplastic small round cell tumor
- 2.9 Other
- Mesothelial tumors
- 3.1 Benign
- 3.1.1 Adenomatoid tumor
- 3.2 Malignant
- 3.2.1 Epithelioid mesothelioma
- 3.2.2
Sarcomatoid mesothelioma Desmoplastic mesothelioma
- 3.2.3
Biphasic mesothelioma
- 3.3 Other
- Miscellaneous tumors
- 4.1 Hamartoma
- 4.2 Sclerosing hemangioma
- 4.3 Clear cell tumor
- 4.4 Germ cell neoplasms
- 4.4.1 Teratoma, mature
- 4.4.2 Teratoma, immature
- 4.4.3 Other germ cell tumors
- 4.5 Thymoma
- 4.6 Melanoma
- 4.7 Others
- Lymphoproliferative diseases
- 5.1
Lymphoid interstitial pneumonia
- 5.2
Nodlar lymphoid hyperplasia
- 5.3
Low-grade marginal zone B-cell lymphoma of the mucosa-associated
lymphoid tissue
- 5.4
Lymphomatoid granlomatosis
- Secondary tumors
- Unclassified tumors
- Tumor-like lesions
- 8.1 Tumorlet
- 8.2 Multiple meningotheloid nodules
- 8.3 Langerhans’ cell histiocytosis
- 8.4 Inflammatory pseudotumor (inflammatory myofibroblastic tumor)
- 8.5 Organizing pneumonia
- 8.6 Amyloid tumor
- 8.7 Hyalinizing granuloma
- 8.8 Lymphangioleiomyomatosis
- 8.9 Multifocal micronodular pneumocyte hyperplasia
- 8.10 Endometriosis
- 8.11 Bronchial inflammatory polyp
- 8.12 Others
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Footnotes
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Abbreviations: CEA = carcinoembryonic antigen; EGFR =
epidermal growth factor receptor; NCAM = neural cell adhesion molecule;
WHO = World Health Organization
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Abstract
Histopathology of Invasive Lung...
