Typical carcinoid tumors of the lung represent the most well differentiated and least biologically

aggressive type of pulmonary NET. These tumors characteristically grow slowly and tend to
metastasize infrequently.

Atypical carcinoid tumors have a more aggressive histologic and clinical picture. They
metastasize at a considerably higher rate than do typical carcinoid tumors and, therefore, carry
a worse prognosis.

Carcinoid syndrome has been reported in association with very large bronchopulmonary
carcinoid tumors or in the presence of metastatic disease. It is noted much less frequently in
association with carcinoids of pulmonary origin than those originating within the gastrointestinal
(GI) tract.

Anatomy
Gross anatomic features of carcinoid tumors include the following:
Tumors most commonly are found within the cartilaginous portion of the tracheobronchial
tree
Tumors usually are soft masses covered with intact bronchial epithelium
Tumors are very vascular and pink-to-purplish in color
Tumors usually are attached to the bronchus by a broad base but occasionally are polypoid
with a distinct stalk
Tumors may be associated with the presence of tumorlets (small foci of atypical
hyperplastic bronchial epithelium in adjacent locations), which may represent local
metastatic disease or an entirely different histologic abnormality and, when present, may
indicate a more aggressive tumor and a poorer prognosis

Pathophysiology
Local
Between 25% and 39% of patients with a carcinoid pulmonary tumor are asymptomatic.
The vast majority of symptomatic patients have symptoms directly involving the
bronchopulmonary tree. Carcinoids developing within large airway structures grow slowly and
can become quite large. Because of their location and size, these central carcinoids can cause
bronchial obstruction. All of the sequelae resulting from bronchial obstruction can follow,
including persistent atelectasis, recurrent pneumonia, pulmonary abscess, and bronchiectasis.

Carcinoids characteristically are vascular tumors and can bleed secondary to bronchial irritation.
Although most tumors are broad-based intrabronchial lesions, a few present on a mobile stalk
and have a polypoid appearance. If large enough, this latter form can create a ball-valve
mechanism within the bronchus, producing hyperinflation in the pulmonary parenchyma distal to
the tumor.

Peripheral pulmonary carcinoid tumors most often are asymptomatic and usually are discovered
incidentally. They are one of the differential diagnoses considered in evaluation of a solitary
pulmonary nodule.

Atypical carcinoid tumors can present in the same locations as typical carcinoids, but they occur
more commonly as peripheral lesions. At least 50% of pulmonary atypical carcinoid tumors
present in the periphery of the lung. They have a more aggressive nature and a greater
tendency to metastasize. [3]
Systemic
As NETs, carcinoids are capable of producing a variety of biologically active peptides and
hormones, including serotonin, adrenocorticotropic hormone (ACTH), antidiuretic hormone
(ADH), melanocyte-stimulating hormone (MSH), and others.

Excess serotonin production has been implicated in the development of carcinoid syndrome.
This syndrome is characterized by a constellation of symptoms, including tachycardia, flushing,
bronchoconstriction, hemodynamic instability, diarrhea, and acidosis, and is reported in 2-12%
of patients with bronchial carcinoid tumors. This syndrome characteristically occurs in the
presence of metastatic disease to the liver; however, bronchial carcinoid tumors, especially
large ones, are capable of producing the syndrome in the absence of metastatic disease.

Ectopic production of ACTH and Cushing syndrome have been reported in association with
typical and atypical carcinoid tumors. Although fewer than 1% of pulmonary carcinoid tumors
produce Cushing syndrome, it is the second most common neuroendocrine syndrome produced
by these tumors. In addition, these tumors are responsible for the development of about 1% of
cases of Cushing syndrome. When a patient is found to have an ectopic source of ACTH
production, the lesion is generally a pulmonary neoplasm of some type.

The syndrome of inappropriate AVP (arginine vasopressin) secretion or syndrome of

inappropriate secretion of ADH (SIADH) can be produced by pulmonary carcinoid tumors,
though it more commonly is associated with small cell lung carcinoma. The production of excess
circulating AVP creates hyponatremia secondary to water retention. Patients present with
weight gain, weakness, lethargy, and mental confusion and, in severe cases, can develop
convulsions and coma.

Etiology
In the past, pulmonary carcinoid tumors were believed to be derived from neural crest cells;
however, they currently are understood to be of endodermal origin, arising from stem cells of the
bronchial epithelium known as Kulchitsky cells.

Although these neoplasms are capable of producing a variety of substances, including

biologically active peptides and hormones, most are inactive.
Unlike carcinoma of the lung, no external environmental toxin or other stimulus has been
identified as a causative agent for the development of pulmonary carcinoid tumors.

Epidemiology

The GI tract is the most common area in which carcinoid tumors most commonly arise.
Bronchopulmonary carcinoid tumors are reported to represent about 10% of all carcinoid
tumors. Between 1% and 6% of all lung tumors are carcinoid tumors. Some 80-90% of tumors
develop within a bronchus of subsegmental size or greater. About 10-15% of tumors arise in a
mainstem bronchus; however, they rarely appear in the trachea. About 10-20% of tumors are
located in the pulmonary periphery.

Atypical carcinoid tumors account for about 10% of all pulmonary carcinoid tumors. Carcinoid
syndrome occurs in about 2% of cases of pulmonary carcinoid tumors, much less frequently
than it does in cases associated with GI carcinoid tumors. [3]
The average age of people at occurrence of typical carcinoid tumors is 40-50 years, but typical
carcinoid tumors have been reported in virtually every age group. Atypical carcinoid tumors
appear in slightly older people than typical carcinoids do. Carcinoid tumors occur in equal
numbers of males and females.

Prognosis
Carcinoid tumors of the lung generally have a better prognosis than other forms of pulmonary
malignancy. They have an overall 5-year survival rate of 78-95% and a 10-year survival rate of
77-90%.

Typical carcinoid tumors have been found to have a much better prognosis than do the atypical
variety. [4] Atypical carcinoid tumors have been associated with a 5-year survival rate of 40-60%
and a 10-year survival rate of 31-60%, depending on the series.

Regardless of histologic type, the presence of lymph node metastases at the time of resection
has a significant effect on prognosis in many series, [5] producing 5-year survival rates of 37-80%
and 10-year rates of 22-80%. This wide variation is likely related to the percent of atypical
carcinoid tumors present in each analyzed series. N1 disease does not affect prognosis in
typical carcinoids, and it tends to decrease survival in atypical carcinoids; however, N2 disease
has a dismal prognosis. [6]

The presence of tumorlets associated with the primary tumor appears to worsen the prognosis.
In a retrospective single institution study from Australia, age greater than 60 years and atypical
histology were negative predictors of survival; patients in the atypical subgroup were found to be
significantly older. [7] Whether or not tumor size is a prognostic risk factor is uncertain.
The presence of carcinoid syndrome or other paraneoplastic syndromes in the absence of
lymph node or distant metastases does not seem to affect prognosis adversely. [8, 9, 10, 11, 12]

History and Physical Examination

About 25% of patients with pulmonary carcinoid tumors are asymptomatic at the time of
discovery.

In symptomatic patients, the most common clinical findings are those associated with bronchial
obstruction, such as persistent cough, hemoptysis, and recurrent or obstructive pneumonitis.
Wheezing, chest pain, and dyspnea also may be noted.

Although uncommon, various endocrine or neuroendocrine syndromes can be initial clinical

manifestations of either typical or atypical pulmonary carcinoid tumors. Carcinoid syndrome,
hypercortisolism and Cushing syndrome, inappropriate secretion of antidiuretic hormone (ADH),
increased pigmentation secondary to excess melanocyte-stimulating hormone (MSH), and
ectopic insulin production resulting in hypoglycemia are some of the endocrinopathies that can
be produced by a pulmonary carcinoid tumor in a patient who is otherwise asymptomatic.

In cases of malignancy, the presence of metastatic disease can produce weight loss, weakness,
and a general feeling of ill health. Carcinoid syndrome is observed most commonly when
metastatic disease to the liver is present.

Laboratory Studies
No biochemical study exists that can be used as a screening test to determine the presence of a
carcinoid tumor or to diagnose a known pulmonary mass as a carcinoid tumor. Assays of
specific hormones or other circulating neuroendocrine substances may establish the existence
of a clinically suspected syndrome produced by a carcinoid tumor.
Assay of 5-hydroxyindoleacetic acid (5-HIAA), a breakdown product of serotonin metabolism, is
only of value if carcinoid syndrome is suspected clinically in an individual with a pulmonary
tumor. The practitioner should perform further diagnostic evaluation for metastatic disease,
particularly hepatic involvement.
Whereas one or several hormone or peptide assays (eg, adrenocorticotropic hormone [ACTH],
melanocyte-stimulating hormone [MSH], or growth hormone [GH]) may be elevated secondary
to ectopic production by a pulmonary carcinoid tumor, serum assays of these substances are
not warranted unless clinical symptoms associated with them are present.
In the vast majority of these (rare) cases, the patient initially presents with the symptoms
produced by ectopic hormone production. After serum assays are performed to confirm that
elevated serum levels of the culprit hormone are present, a search begins for the source of the
ectopic hormone production. If the pituitary gland and appropriate endocrine organs are ruled
out as the source, ectopic sources are sought.
At this point in the workup, a carcinoid tumor or other pulmonary neoplasm may be found. This
latter point especially is true because many cases of pulmonary carcinoid tumors that cause
ectopic hormone production are small peripheral lesions and often are not readily found on
initial plain chest radiograph. [13]

Imaging Studies
Chest radiography
An abnormal finding on chest radiography (see the images below) is present in about 75% of
patients with a pulmonary carcinoid tumor. Findings include either the presence of the tumor
mass itself or indirect evidence of its presence observed as parenchymal changes associated
with bronchial obstruction from the mass. Changes associated with bronchial obstruction include
persistent atelectasis, consolidation secondary to pneumonia, and changes of bronchiectasis
and hyperinflation.
Computed tomography
High-resolution computed tomography (CT) is the best type of CT examination to obtain for
evaluation of a pulmonary carcinoid tumor. It can demonstrate more detail about nodules,
masses, or suspicious parenchymal changes, such as persistent atelectasis or obstructive
pneumonia found on plain chest radiography (see the image below). It may reveal nodules or
masses that are not well visualized on plain chest radiography by virtue of their small size or
their position, such as those located in a retrocardiac position.
In the evaluation of a solitary pulmonary nodule, CT can provide specific information about
pulmonary nodules, such as size, position within the lung, density, and edge configuration. The
presence and distribution of calcium within a nodule also can be readily observed on CT.
Certain pulmonary nodules possess characteristic calcium distributions, the identification of
which can strongly suggest that the nodule is benign or malignant. Carcinoid tumors of the lung
often possess some calcifications, though no characteristic pattern is known.
High-resolution CT can reveal the presence of an air bronchogram within a pulmonary nodule, a
finding that indicates the intimate relation of the tumor and the tracheobronchial tree. This
feature may indicate that the lesion is more likely to be malignant. Because the majority of
carcinoid tumors are intrabronchial, this should be a common feature of carcinoid tumors on CT.
Intravenous (IV) contrast in CT also can be useful in differentiating malignant from benign
lesions. Malignant lesions generally have increased vascularity and show greater enhancement
than benign lesions on contrast CT. Because carcinoid tumors are highly vascular, they also
possess this feature.
In a 2011 report on CT features, peripheral carcinoid tumors presenting as solitary pulmonary
nodules were found to have lobulated nodules of high attenuation with contrast enhancement;
densely enhanced nodules with contrast administration; calcification; subsegmental airway
involvement on thin-section analysis; and nodules associated with distal hyperlucency,
bronchiectasis, or atelectasis. [14]
Magnetic resonance imaging
Magnetic resonance imaging (MRI) generally provides information similar to that provided by
CT. Dynamic MRI may be a useful complimentary examination in selected cases. [15]
Positron emission tomography
Positron emission tomography (PET) makes use of the fact that malignant cells possess a
higher metabolic activity rate than healthy cells do. [16] A tagged glucose molecule, FDG (2-
[fluorine-18]-fluoro-2-deoxy-D-glucose), is administered, and metabolic analysis of this
substance within the cells of the imaged organ system or the whole body is conducted.
PET appears to have considerable sensitivity and specificity for the identification of malignant
lesions.
Although highly vascular, carcinoid tumors of the lung do not show increased metabolic activity
on PET and would be incorrectly designated as benign lesions on the basis of findings from this
study.
Radionuclide studies
Somatostatin receptors are present in many tumors of neuroendocrine origin, including
carcinoid tumors. Nuclear imaging with somatostatin analogues reveals increased tracer activity
in these tumors and their metastases. [17]
This study is excellent for evaluation of the thorax and mediastinum. One drawback to this type
of study is the fact that some uptake of the tracer typically occurs in a number of organs,
including the liver, thyroid, kidneys, and spleen; thus, lesions in these areas may be
obscured. [18, 19]

Diagnostic Procedures
Bronchoscopy
About 75% of pulmonary carcinoids are visible on bronchoscopy. In most cases, the physician
makes the diagnosis of pulmonary carcinoid tumor on the basis of the findings from
bronchoscopy plus a combination of radiologic studies.
Severe hemorrhage has been reported in association with biopsy of a bronchial carcinoid tumor
during bronchoscopy. Although these are vascular tumors, the vast majority of reports of severe
hemorrhage associated with them are related to attempts at partial or total removal at the time
of bronchoscopy.
At present, most endoscopists perform bronchoscopic biopsy of these lesions for histologic
diagnosis. Because these masses are located beneath the bronchial epithelial layer, deeper
biopsies may be required than for other types of bronchial neoplasms. Some endoscopists have
a dilute solution of epinephrine available to apply to the biopsy site for vasoconstriction. Others
advocate obtaining a biopsy of these tumors with general anesthesia and rigid bronchoscopy.
Transbronchial fine-needle biopsy
Transbronchial fine-needle biopsy of a submucosal carcinoid mass may be performed, though
the small amount of tissue obtained may make histologic analysis challenging. Both typical and
atypical carcinoid tumors share a number of histologic characteristics with small cell carcinoma
of the lung, and inadequate sampling, especially in frozen section analysis, may increase the
likelihood of misdiagnosis. Fortunately, permanent pathologic examination using hematoxylin
and eosin stains and others is used to establish the correct diagnosis in the vast majority of
cases.
Transthoracic needle biopsy
Percutaneous needle biopsy may be useful for tissue sampling of peripheral pulmonary
nodules.
As with transbronchial biopsy, the amount of tissue sampled may be quite limited, making exact
histologic determination difficult.
The diagnostic yield for a specific benign diagnosis in solitary pulmonary nodules is 12-68%.
Nonspecific diagnosis in the absence of malignant cells does not confirm benignity. The
negative predictive value of this procedure to exclude malignancy in solitary pulmonary nodules
is reported to be 52-88%.
A negative finding on biopsy should not produce a false sense of confidence in the examining
physician. A combination of clinical findings, patient risk factors, and data from all completed
diagnostic studies should enter into the decision whether to proceed with surgical removal of a
pulmonary nodule or to observe it for a longer period. If a suspicion of malignancy exists despite
a negative finding on transthoracic biopsy, surgical excision of the nodule and pathologic
analysis should be undertaken.

Histologic Findings
Typical carcinoid tumors
In typical carcinoid tumors, cells tend to group in nests, cords, or broad sheets. Cell groupings
can take on a glandular or alveolar configuration. Arrangement is orderly, with groups of cells
separated by highly vascular septa of connective tissue.
Individual cell features
In pulmonary carcinoid tumors, cells are small and polygonal. They have finely granular
eosinophilic cytoplasm, which can range from clear to deeply eosinophilic. Nuclei are small and
round. Mitoses are infrequent. Spindle-shaped cells are an accepted variant, especially in
peripherally located tumors.
Electron microscopic and immunohistochemical features
Well-formed desmosomes and abundant neurosecretory granules are present. Many pulmonary
carcinoid tumors stain positive for a variety of neuroendocrine markers (eg, serotonin, gastrin,
MSH, vasopressin, bombesin, somatostatin, and neuron-specific enolase [NSE]), though this
staining does not correlate with clinical activity. Immunostaining with chromogranin A is a useful
study that helps the physician differentiate pulmonary carcinoid tumors, which stain strongly
positive for it, from small cell carcinoma of the lung, which produces negative
results. [20, 13, 21,22, 23, 24]
Atypical pulmonary carcinoid tumors
Atypical tumors have no distinguishing gross characteristics that may be used to differentiate
them from typical carcinoids. In many series, they are reported generally to be larger than
typical carcinoids, but this is not a distinguishing feature. They are located in the periphery of
the lung in about 50% of cases.
Arrigoni identified the chief histologic features that define atypical carcinoid tumors and help the
physician to distinguish them from typical carcinoid tumors. [25] The presence of one or several of
these features is found in tumors identified as atypical pulmonary carcinoid tumors. Features
include the following:
 Increased mitotic activity in a tumor with an identifiable carcinoid cellular arrangement with
roughly one mitotic figure per one or two high-power fields (HPFs)
Pleomorphism and irregular nuclei with hyperchromatism and prominent nucleoli
Areas of increased cellularity with loss of the regular, organized architecture observed in
typical carcinoid
Areas of necrosis within the tumor
Atypical carcinoid tumors have no distinctive electron microscopic features compared to typical
carcinoid tumors. Like other neuroendocrine tumors, they stain strongly for a number of
immunohistochemical markers but have no specific marker exclusive for them.
In a study of pulmonary carcinoid tumor in Korea, Ha et al suggested that lung parenchymal
invasion could be a useful histologic feature for raising suspicion of atypical carcinoid, as well as
for predicting the prognosis of carcinoid tumor. [26]

Staging
At present, staging of pulmonary carcinoid tumors is designated in the same manner as that for
bronchogenic carcinoma of the lung. Whereas typical carcinoid tumors, considered the least
aggressive form, most commonly present as stage I tumors, more than 50% of atypical
carcinoid tumors are found to be stage II (ie, bronchopulmonary lymph node involvement) or
stage III (ie, mediastinal lymph node involvement) at presentation.
The exact determination of the specific histologic entities within the spectrum of pulmonary
neuroendocrine tumors is an area of considerable controversy.
Several authors have renamed the entire spectrum of pulmonary neuroendocrine neoplasms on
the basis of more advanced histologic study. One classification system labels typical carcinoid
tumors as type 1 Kulchitsky cell carcinoma, atypical carcinoids as type 2 Kulchitsky cell
carcinomas, and small cell carcinoma as type 3. Another defines these as well-differentiated,
intermediate cell, and small cell neuroendocrine carcinomas.
Additional changes in tumor classification also have been proposed specifically with respect to
atypical carcinoid tumors. Several subcategories of atypical carcinoid have been described on
the basis of identification of genetic molecular abnormalities.
The addition of genetic marker identification to previous methods of tumor analysis has resulted
in further subclassification for some of the more aggressive types of these neuroendocrine
tumors. Large cell neuroendocrine and mixed small-large cell neuroendocrine carcinomas have
been proposed as high-grade tumors more closely related to small cell carcinoma than to
carcinoids, falling into the disease spectrum between atypical carcinoid and small cell
carcinoma.

Approach Considerations

All pulmonary carcinoid tumors should be treated as malignancies. Because surgical resection
is the only treatment known to achieve cure, all pulmonary carcinoid tumors without evidence of
distant metastatic disease should be resected completely as long as no contraindication to
surgery exists.
Total resection should be the primary goal of any form of surgical therapy. Lymph node
dissection should accompany resection. The most commonly used procedures are formal
lobectomy, segmentectomy, and pneumonectomy, but various parenchymal-sparing
bronchoplastic procedures, including sleeve resections, have also been utilized with good long-
term results. Patients with marginal pulmonary reserve may be good candidates for complete
resection and cure if a bronchoplastic or parenchymal-sparing procedure can be performed.
Thoracoscopic or open wedge resection of a peripheral carcinoid tumor should be reserved for
patients with limited pulmonary reserve who cannot tolerate anatomic resection. Appropriate
lymph node dissection also should be performed in these cases.
Bronchoscopic resection of an intrabronchial carcinoid tumor is recommended only in selected
cases. These include preoperative management of symptomatic bronchial obstruction prior to
formal resection and palliative treatment in patients who would otherwise not tolerate formal
pulmonary resection.
Complete tumor removal is extremely unlikely with this method, because these obstructing
intrabronchial tumors usually have penetrated the bronchus and invaded the local pulmonary
parenchyma by the time they are discovered. In addition, lymph node staging cannot be
accomplished. Palliation, not cure, is the goal of this technique.
Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser photoresection of intrabronchial carcinoid
tumors also has been proposed. This form of therapy should not be considered primary and
should be reserved for use in the same types of cases for which bronchoscopic resection is
indicated.
The limitations of laser photoresection are similar to those of bronchoscopic resection, with one
additional drawback. Transbronchial photocoagulation destroys at least a portion of the resected
tumor and thwarts thorough analysis of a completely resected specimen. Incomplete specimen
analysis may have significant bearing on prognostic determination because the histologic
features of pulmonary carcinoid tumors must be scrutinized carefully in order to determine
whether typical or atypical carcinoid is present.
Resection of distant metastatic lesions is indicated in a select group of patients in whom
thorough evaluation has revealed isolated lesions in areas amenable to resection.
Formal resection of carcinoid tumors of the lung only is contraindicated in patients who would
not otherwise tolerate the operative procedure or who are found to have widespread metastatic
disease.
Medical Therapy
No medical therapy exists for the primary treatment of carcinoid tumor of the lung.
Chemotherapy and radiation therapy have been used in the treatment of metastatic disease but
have met with virtually no success. A response rate of 30-35% has been reported with a
combination of 5-fluorouracil and streptozotocin. Symptomatic relief of carcinoid syndrome from
metastatic disease has been achieved with octreotide, which can be administered
subcutaneously.
In February 2016, everolimus was approved by the US Food and Drug Administration (FDA) for
progressive, well-differentiated, nonfunctional neuroendocrine tumors (NETs) of lung origin that
are unresectable, locally advanced, or metastatic. Approval was based on the RADIANT-4 trial,
in which median progression-free survival was 11 months in the 205 patients allocated to
receive everolimus (10 mg/day) and 3.9 months in the 97 patients who received placebo.
Everolimus was associated with a 52% reduction in the estimated risk of progression or
death. [27]
Surgical Therapy
Surgical resection is the primary mode of therapy for carcinoid tumors of the lung. Various forms
of resection have been utilized successfully and with excellent long-term results.
Some 40-50 years ago, in an era when these tumors were considered more benign in their
activity, bronchotomy with local excision of the tumor mass was used for resection of carcinoid
tumors located in larger bronchial structures. Within the past two decades, a greater
understanding of the malignant nature and biologic activity of these tumors has been acquired,
and surgical resection has become more radical, now more closely resembling that for primary
carcinoma of the lung.
At present, anatomic lobectomy is the most commonly performed procedure for resection of
pulmonary carcinoid tumors. Larger or more proximal lesions may require bilobectomy or
pneumonectomy. Smaller lesions in peripheral locations and contained within a single
pulmonary segment may be treated with segmentectomy or wedge resection.
Because of the intrabronchial location and slow rate of growth of most carcinoid tumors, a
variety of parenchymal-sparing procedures, including sleeve lobectomy and sleeve
pneumonectomy, have been proposed and performed successfully with excellent long-term
results.
In a large review of the Surveillance Epidemiology and End Results (SEER) database, sublobar
resection of carcinoid tumors was not found to compromise oncologic outcomes; rather, factors
such as age, sex, race, stage, and histologic types were direct influences on survival rates and
the likelihood of patients acquiring other types of cancer. As long as complete resection and
adequate mediastinal staging are performed, it is not necessary to perform a lobectomy on
typical carcinoid tumors. [28]
There is a resurgence of interest in local resection of carcinoid tumors. Most of these local
resections are bronchoplastic procedures without any parenchymal resection, in which the
section of bronchus containing the tumor is excised and the divided ends of the bronchus are
reanastomosed.
A renewal of the use of bronchotomy and local excision has been proposed for specific
carcinoid tumors that are polypoid in configuration. Regional lymph node dissection at the time
of primary tumor resection is advocated by an increasing number of authors for both staging
and treatment. A number of patients in several series had a favorable long-term outcome after
resection of pulmonary carcinoid tumors and regional lymph nodes, even when lymph node
metastases were present. [29]
Because of their more biologically aggressive nature, greater tendency to metastasize, and
poorer general prognosis, it is recommended that atypical carcinoid tumors be treated very
aggressively. In general, the same surgical approach should be used for these aggressive forms
of carcinoid as for cases of pulmonary carcinoma; this includes radical resection with frozen
section evidence of tumor-free bronchial margins plus hilar and mediastinal lymphadenectomy.
Wedge resection of small peripheral typical carcinoid tumors without evidence of lymph node
metastases may be acceptable in selected cases; however, a more radical resection is
indicated for a similar mass found to be atypical.
Bronchoscopic resection using an Nd:YAG laser, with or without photodynamic therapy, also
has been utilized in selected cases. As yet, these forms of treatment have been reserved for
preresection reduction of intrabronchial tumor mass or for palliative management of airway
obstruction in cases where the patient was considered otherwise inoperable.
In the former case, this form of treatment is helpful in reducing bronchial obstruction and
clearing postobstructive pneumonia before formal surgical resection. In addition, some experts
believe that preresection tumor reduction may allow a more conservative surgical resection. To
date, series utilizing this form of therapy have been quite small, and long-term results have yet
to be determined. This area has been controversial. [8, 30]
Preparation for surgery
The surgeon must have a clear preoperative understanding of the location of the tumor
(particularly if it is intrabronchial) and, to the degree possible, its extent. Many surgeons
revisualize the tumor with the bronchoscope in the operating room immediately prior to the
resection. This may facilitate decision-making regarding the choice of surgical procedure.
Preoperative evaluation of patients for resection of carcinoid tumors is identical to that for those
with carcinoma of the lung.
Evaluation of pulmonary function should be performed prior to any procedure that may require
resection of a portion of lung tissue. The same pulmonary function criteria used for patients
undergoing pulmonary resection for any other reason applies to individuals having surgery for
carcinoid tumors.
Because tissue-sparing procedures can be performed for some carcinoid tumors that are
contained entirely within a bronchial structure, the limits of acceptable postoperative pulmonary
reserve may be extended for patients with marginal pulmonary function in these cases.
However, such procedures should be performed by thoracic surgeons experienced in
bronchoplastic techniques.
Cardiac function should be assessed before any intrathoracic procedure.
Only obtain blood or serum assay of serotonin or 5-hydroxyindoleacetic acid (5-HIAA) if
carcinoid syndrome is suspected clinically. If this study result is positive, further metastatic
workup, especially evaluation for hepatic metastases, should be performed. Evidence of distant
metastases often alters the decision about resection.
Operative details
Evaluation of the extent of local disease and the existence of nodal disease must be performed
so that the proper choice of procedure can be made. This is especially important in
bronchoplastic cases and parenchymal-sparing procedures.
In cases where a solitary pulmonary nodule is resected, accurate frozen section diagnosis is
important because the extent of the subsequent resection may vary, depending on the histologic
findings. A small, peripheral typical carcinoid tumor may be treated with a more conservative
resection, while an atypical carcinoid tumor requires a more radical resection. Hilar and
mediastinal nodes also should be sampled and resected if necessary.
Operative procedures are conducted in much the same fashion as other pulmonary resections.
At most major centers, a double-lumen endotracheal tube is used to allow single-lung ventilation
and facilitate visualization of the surgical field. Intra-arterial monitoring lines are placed for
continuous blood pressure monitoring. Continuous transcutaneous oxygen saturation and end-
tidal carbon dioxide monitoring are routine.
Careful intraoperative management of fluids is extremely important to avoid fluid overload and
pulmonary edema in lung resection cases, especially pneumonectomy. A preoperative
understanding between the surgeon and anesthesiologist to limit crystalloid infusion and
maintain the patient in a relatively even fluid balance is advisable.
When not contraindicated, placement of an epidural catheter, ideally in the thoracic position, for
postoperative pain management is advisable. If this is not possible, an intercostal block using a
longer-acting local anesthetic, such as bupivacaine, is helpful for immediate postoperative pain
control, though its effective duration is not longer than 4-6 hours.
Postoperative Care
Postoperative management is identical to that employed for any patient undergoing pulmonary
resection for any reason.
In the vast majority of cases, discontinuance of assisted ventilation and extubation is possible at
the completion of surgery or very shortly thereafter. Most patients who undergo pulmonary
resection do not require postoperative ventilation, though patients with significant chronic
obstructive pulmonary disease (COPD) or other diseases associated with marginal pulmonary
function may require it.
Patients who undergo any formal pulmonary resection or thoracotomy without major resection
should be placed in an intensive care setting for at least 24 hours. Intensive care monitoring
may not be needed for those who undergo less invasive procedures, such as thoracoscopic
biopsy, but this should be decided on an individual basis.
A chest radiograph should be obtained immediately after surgery in the recovery room or
intensive care unit (ICU) and daily thereafter. Additional films are warranted if any change in
pulmonary status occurs in the course of recovery. A chest radiograph should be obtained
immediately after thoracostomy tubes are removed.
Chest tube patency must be maintained, and constant suction with 20 to 25 cm under
H2O seal suction should be established. Chest tubes are removed when the lung is fully
expanded on chest radiograph and no evidence of air leak exists.
Pulmonary toilet and pain management are vital for successful management. Incentive
spirometry and assisted coughing at scheduled intervals can be very helpful for prevention of
atelectasis and clearing of secretions. Nasotracheal suctioning may be required in some
patients for aspiration of secretions and to stimulate an effective cough effort. If atelectasis is
significant or major amounts of secretions cannot be cleared, bronchoscopy may be needed.
Other forms of pulmonary toilet, such as chest physiotherapy or intermittent positive-pressure
breathing, have variable results in patients who undergo pulmonary resection.
Pain management via epidural catheter is ideal in these patients because this method controls
pain well without altering the sensorium or diminishing the respiratory effort of the patient as
significantly as IV narcotics may. If epidural analgesia is not possible, patient-controlled
analgesia (PCA) with well-defined parameters may be used, though it may not be as effective.
The judicious fluid management begun in the operating room should be continued in all patients
who undergo a major resection. Volume overload must be avoided. If excessive fluids were
administered during the operative procedure, administration of a diuretic may be needed.
If the volume status of a postoperative patient is in question or if cardiac disease is present,
placement of a pulmonary artery catheter may be necessary. Some surgeons advise performing
this procedure with fluoroscopic guidance after major lung resection to assure proper positioning
of the catheter into the nonoperated pulmonary artery.
Postoperative ileus is not common in patients who undergo pulmonary surgery; consequently,
oral fluids often can be administered within 24 hours. Maintenance IV fluids should be all that
are required until oral intake is adequate, and IV fluids should be discontinued thereafter.
Because airway structures containing secretions and bacteria are divided in pulmonary surgical
cases, most surgeons administer a broad-spectrum antibiotic preoperatively and for 2-3 days
postoperatively. This coverage is administered primarily to reduce the risk of infection within the
pleural space. Wound infections in thoracotomy patients are quite rare.
Complications
Complications that can arise after surgery for resection of pulmonary carcinoid tumors are
similar to those that may occur after pulmonary resection for other reasons. In the immediate
postoperative period, bleeding, atelectasis, and prolonged air leak are the most common
complications.
Bleeding
Bleeding generally is an early postoperative complication and most often manifested is by
copious or persistent amounts of blood from the thoracostomy tubes.
In some cases, the measured amount of bleeding from the chest tubes does not itself appear to
herald a problem. Other clinical signs (eg, hypotension, tachycardia, decreased urine output, or
inordinately low hematocrit) in the immediate postoperative period may alert the physician to
significant undrained blood loss. In such cases, chest tubes may not be in proper position for
drainage or may be partially clotted, preventing complete evacuation of the chest. A retained
hemothorax in these cases is evident on chest radiograph.
Bleeding that is massive, requires large amounts of crystalloid or blood replacement to maintain
hemodynamic stability, or is persistent over a number of hours and indicates that re of the
thorax is needed.
Atelectasis
Some degree of atelectasis is present postoperatively in all patients undergoing chest surgery.
Adequate pain control and vigorous pulmonary toilet are mandatory in order to avoid major
problems with atelectasis. If the patient is unable to clear his or her own secretions adequately,
nasotracheal suctioning is an effective method of assisting the patient. Bronchoscopy may be
used for clearing secretions if nasotracheal suction is unsuccessful or if major areas of lung are
collapsed.
Air leak
Air leak is a common postoperative problem after pulmonary resection and usually is produced
by the raw surfaces of the lung parenchyma that are created during resection, such as the area
in the major fissure. In the vast majority of cases, if the lung is fully expanded on chest
radiography, air leak diminishes over a period of a few days and ceases. Persistent air leak is a
frustrating problem and may result from a number of causes, including the following:
Persistent air leak may be caused by a leak within the chest tube drainage system or
improper positioning of the chest tube within the thorax; for example, when some of the
chest tube openings are located outside of the pleural space, there may appear to be an air
leak when none is present
Incomplete reexpansion related to persistent atelectasis may be the cause of persistent air
leak
In individuals with underlying restrictive lung disease, the remaining lung may not be able to
expand enough to completely fill the thoracic space
Pulmonary resection performed on a lung that has significant emphysematous changes
also can result in prolonged air leak
Unlike the leaks that are from the raw, resected parenchymal surface, more serious air leaks
arise from lesser bronchial structures within the raw parenchymal tissue in the area of resection
or from the bronchial stump or anastomosis itself. These usually persist as leaks of significant
volume and may be associated with an incompletely expanded lung on chest radiograph.
Bronchial stump disruption may present as a pneumothorax on chest radiograph or as a new air
leak at an interval after surgery, usually about 5-8 days postoperatively. This picture also may
be present if a leak occurs at the bronchial anastomosis of a sleeve resection of other
bronchoplastic procedures.
Large, prolonged air leaks producing some degree of persistent collapse of the lung usually
require reoperation for closure. Thoracoplasty may be considered in cases in which a leak
persists in the face of restrictive lung disease.
Postoperative respiratory insufficiency
Postoperative respiratory insufficiency is a devastating postoperative complication that, at best,
may result in the patient becoming pulmonologically crippled with extremely limited functional
reserve and, at worst, may necessitate some permanent form of ventilatory support.
This complication largely can be avoided by prudent preoperative examination of the pulmonary
function and circulatory status of the patient. By doing this, the vast majority of individuals who
would not have sufficient pulmonary reserve after the required resection are identified in
advance and not subject to this devastating complication.
Postoperative pulmonary edema usually related to injudicious administration of intravenous
fluids represents one cause of respiratory insufficiency. This can be a very serious, even lethal,
postoperative problem that must be addressed aggressively when found.
A variety of other factors also must be noted in patients who are difficult to weaning from
ventilatory support or oxygen post resection. Full lung or lobar expansion must be present and
no residual pneumothorax present. Lung condition must be optimal and without infection, and
pain management must be adequate.
Slow weaning from the ventilator may be required; if this is successful, long-term oxygen
therapy still may be required.
Pleural infection and empyema
Postoperative intrathoracic infections almost always are related to the presence of a
bronchopleural fistula. The diagnosis can be made by means of culture of the pleural fluid.
Complete lung expansion must accompany adequate drainage of the space for successful
resolution of this problem. Adequate drainage by means of properly placed thoracostomy tubes
or ultrasound- or computed tomography (CT)-guided aspiration may be successful, but
reoperation for clearance of the infection and decortication and, if necessary, closure of the
fistula may be indicated. Various thoracoplasty techniques can be employed to reduce the size
of the thorax if full expansion of the remaining lung cannot completely fill the space.
Infection in the postpneumonectomy space is a true challenge and may require a Clagett
procedure or the rotation of chest wall muscle flaps into the chest to obliterate the thoracic
cavity after the empyema is drained.
Cardiac arrhythmias
Atrial fibrillation or flutter is a well-known complication after pneumonectomy or upper
lobectomy, especially in older patients. Prompt identification of the arrhythmia and appropriate
medical management is indicated. Electrical cardioversion may be required if the patient is
unstable.
Some surgeons administer digitalis to their patients preoperatively in an attempt to avoid this
complication. If this is instituted, patients should be fully digitalized and on maintenance therapy
with laboratory evidence of therapeutic digitalis levels before the surgical procedure. An attempt
at rapid digitalization 24-48 hours before operation usually is not effective.

Long-Term Monitoring
After discharge from the hospital, surgical follow-up for observation of wound healing and
determination that no intrathoracic complication has occurred is conducted for 8-12 weeks.
Oncologic follow-up is conducted in a fashion similar to that for pulmonary carcinoma after
resection. Patients' cases are followed clinically and with plain chest radiography every 2-3
months for the first year after surgery. If no evidence of recurrence is discovered within this
period, surveillance intervals are extended to every 6 months. Additional studies, such as CT,
are performed only if suspicion of recurrence arises.
With respect to postoperative surveillance, a multi-institutional study showed that recurrence
was rare in typical carcinoids. [31] Recurrence is more common in atypical carcinoids (26%),
yet most recurrences were not detected by routine surveillance protocols; instead, they
appeared either after symptoms developed or incidentally on studies done for other reasons.
Hence, there are no set recommendations for routine follow-up in patients with pulmonary
carcinoid after surgical treatment