The new england journal of medicine

case records of the massachusetts general hospital

Founded by Richard C. Cabot

Nancy Lee Harris, m.d., Editor
Jo-Anne O. Shepard, m.d., Associate Editor Stacey M. Ellender, Assistant Editor
Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor

Case 26-2004: A 56-Year-Old Woman

with Cough and a Lung Nodule
Thomas J. Lynch, M.D., Cameron D. Wright, M.D., Noah C. Choi, M.D.,
Suzanne L. Aquino, M.D., and Eugene J. Mark, M.D.

presentation of case

Dr. Jennifer Temel (Medical Oncology): A 56-year-old woman was evaluated in the thoracic From the Departments of Medical Oncol-
oncology clinic for treatment of nonsmall-cell lung cancer. ogy (T.J.L.), Thoracic Surgery (C.D.W.), Radi-
ation Oncology (N.C.C.), Radiology (S.L.A.),
The patient had been in her usual state of good health until three months before and Pathology (E.J.M.), Massachusetts
presentation, when a nonproductive cough developed. During the next two months, General Hospital; and the Departments of
the cough became productive of yellow, blood-tinged sputum. She saw her primary care Medicine (T.J.L.), Surgery (C.D.W.), Radia-
tion Oncology (N.C.C.), Radiology (S.L.A.),
physician, and a chest radiograph revealed a nodule, 2.5 cm in diameter, in the upper and Pathology (E.J.M.), Harvard Medical
lobe of the right lung (Fig. 1A). Computed tomographic (CT) scanning of the thorax School.
identified a 2.5-cm nodule in the right upper lobe, with no enlarged hilar or mediastinal
N Engl J Med 2004;351:809-17.
lymph nodes (Fig. 1B). An abdominal ultrasound examination, a CT scan of the head, Copyright 2004 Massachusetts Medical Society.
and a bone scan showed no abnormalities. A positron-emission tomographic (PET) scan
revealed increased accumulation of fludeoxyglucose F 18 at the apex of the right lung,
at a site corresponding to the primary lesion (Fig. 1C); no other areas of accumulation
were noted.
One month before the patients evaluation in the clinic, bronchoscopy and mediasti-
noscopy were performed in preparation for a thoracotomy and resection of a suspected
bronchogenic carcinoma. Bronchoscopic examination revealed no abnormalities. Medi-
astinoscopy revealed no nodes on the left side but did show a normal-appearing subca-
rinal node and a normal-sized, mobile paratracheal node on the right side. Intraoper-
ative examination of a frozen section of a biopsy specimen of the paratracheal node
showed metastatic nonsmall-cell lung cancer; the subcarinal node was normal. The
thoracotomy was not performed, and the patient was referred to the thoracic oncology
clinic at this hospital.
An aneurysm of the left middle cerebral artery had been repaired three years previ-
ously, and an aneurysm of the right internal carotid artery had been repaired two years
previously. The patient had no neurologic deficits. She had smoked one to two packs of
cigarettes per day for 38 years but had stopped smoking when her cough developed.
She did not drink alcohol. Her only medications were alprazolam as needed for anxiety
and a nicotine patch. She had no family history of lung cancer.
On physical examination, her vital signs were normal and she appeared comfort-
able. There was no palpable lymphadenopathy. The lungs were clear on auscultation.

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 The new england journal of medicine

C D

Figure 1. Radiologic Studies.

A chest radiograph shows a 2.5-cm nodule in the right upper lobe (Panel A). A CT scan confirms the presence of a 2.5-cm
nodule in the right upper lobe on lung windows (Panel B). The surrounding lung tissue shows moderate centrilobular em-
physema. A coronal image from a PET scan obtained with the use of fludeoxyglucose F 18 shows increased metabolic ac-
tivity in the upper-lobe nodule (Panel C) and in the right paratracheal (Panel D, arrow) and subcarinal lymph-node regions.

Neurologic examination revealed no abnormali- and mediastinal contours and densities are normal.
ties. Laboratory-test results were normal, except forA CT scan shows a spiculated nodule in the apex of
a slightly elevated level of alkaline phosphatase the right lung (Fig. 1B). There is centrilobular em-
(116 U per liter). physema of the surrounding lung parenchyma.
There is no evidence of enlarged lymph nodes in the
differential diagnosis right hilum or mediastinum.
PET scanning of the thorax with the use of
Dr. Suzanne L. Aquino: The chest radiograph obtained fludeoxyglucose F 18 shows increased uptake of
at the other hospital shows an ill-defined, 2.5-cm this radioactive agent in the nodule in the right
nodule in the right upper lobe (Fig. 1A). The hilar upper lobe (Fig. 1C) a finding that suggests the

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 case records of the massachusetts general hospital
presence of a malignant tumor. Although it was
not noted at the time, in retrospect it is apparent
that there was an increase in fludeoxyglucose F 18
uptake in the right paratracheal and subcarinal
lymph-node regions (Fig. 1D) a finding that sug-
gests metastatic disease in the lymph nodes. There
are no other areas of increased fludeoxyglucose F 18
uptake. This scanning technique has a sensitivity of
92 to 95 percent and a specificity of 88 to 90 percent
for detecting cancer in pulmonary nodules.1-3 False
negative results may occur in slowly growing tu-
mors, such as bronchioloalveolar carcinomas4 and
carcinoid tumors,5 and in nodules less than 1 cm in
diameter. Any nodule that shows increased uptake
of fludeoxyglucose F 18 should be considered po-
tentially neoplastic, and a biopsy should be per-
formed. Nodules without increased metabolic ac-
tivity should be followed with repeated radiography
to ensure that their size remains stable.
Because PET scanning performed with the use
of fludeoxyglucose F 18 measures the rate of me-
tabolism, other diseases with increased metabolism
can resemble cancer, especially if the lesions have a
nodular appearance. This explains the slightly lower
specificity of the technique for detecting a malig-
nant condition.1-3 False positive interpretations
may occur with granulomas, pneumonias, and in-
flammatory lesions such as rheumatoid nodules.6-9
Since the detection of abnormal lymph nodes on
CT scans is based purely on size, a small lymph
node involved with tumor would be interpreted as
benign if it was less than 1 cm in diameter. PET
scanning performed with fludeoxyglucose F 18 has
improved the radiologic staging of lung cancer, with
a sensitivity of 91 percent, a specificity of 86 percent,
and negative and positive predictive values of 95
percent and 74 percent, respectively.10-13 As with
the detection of a primary tumor, the major limita-
tions are false positive findings in lymph nodes
affected by other diseases, such as silicosis or gran-
ulomatous diseases. Therefore, to confirm the pres-
ence of cancer, most experts recommend biopsy of
any lymph nodes that show increased fludeoxyglu-
cose F 18 uptake.
Dr. Thomas J. Lynch: Dr. Wright, can you tell us
about your surgical approach for this patient?
Dr. Cameron D. Wright: In this clinical setting, I
thought the most likely diagnosis preoperatively
was nonsmall-cell lung cancer. She was of the ap-
propriate age (older than 55 years), had a history of
smoking, had no history of previous inflammatory
lung illness, and had emphysema, hemoptysis, and
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a spiculated, solitary pulmonary nodule, as revealed
on a PET scan. Given these factors, the chance that
her diagnosis was lung cancer was greater than 90
percent.
There are pitfalls for the surgeon in the preoper-
ative assessment of mediastinal lymph nodes. Small
nodes that are considered benign according to CT
criteria can be microscopically positive for cancer,
and large nodes are sometimes only inflammatory.
Enlarged nodes that are pathologically benign are
found most commonly when there is an obstructive
pneumonia caused by a tumor in the bronchus,
usually a squamous-cell cancer. In contrast, large
nodes with peripheral lung lesions almost always
contain cancer. If both the CT scans and the PET
scans are read as negative, it is highly likely that the
nodes will be negative for cancer. If either set of
scans is positive (or if both are), it is necessary to
sample the lymph nodes to obtain a tissue-based
diagnosis. The uncertainty is highlighted in this
case, since the retrospective interpretation of the
PET scan suggested that both the right paratracheal
and the subcarinal nodes were positive but on biop-
sy only the paratracheal node was positive. To as-
certain whether a patient is a candidate for preoper-
ative chemotherapy or radiotherapy, invasive staging
of the mediastinum must be performed.
Since this patients PET scan was originally read
as showing no evidence of metastasis, we planned
a one-day operation consisting of surgical staging of
the mediastinum with a mediastinoscopy, and if the
findings were negative, a thoracotomy. Most nodal
groups that are important in lung cancer14,15
the paratracheal, subcarinal, and tracheobronchial
angle nodes can be readily accessed by a medi-
astinoscopy. Nodes on the left side of the aortic
arch (para-aortic and subaortic) are accessed by an
anterior mediastinotomy, which can be done at the
same time. It is now possible, when necessary, to
access the inferior mediastinal nodes by endoscopic
fine-needle aspiration guided by ultrasonography.
The staging of lung cancer is based on the size
of the tumor (T1 through T4), the location and num-
ber of positive lymph nodes (N0 through N3), and
the absence or presence of distant metastases (M0
or M1). This patient has a tumor that is T1 (diame-
ter, <3 cm, without invasion of the pleura), N2 (in-
volvement of ipsilateral, mediastinal, and subcari-
nal lymph nodes), and M0 (no distant metastases).
Lung cancer is also staged as IA or IB, IIA or IIB,
IIIA or IIIB, or IV, depending on the combination of
TNM findings. This patients tumor is considered
august 19, 2004 811
 The new england journal of medicine

locally advanced (stage IIIA). The expected one-year

and five-year survival rates for this patient are 64 A
percent and 23 percent, respectively.16
There are several prognostic factors in stage N2
lung cancer, but the most important consideration
is whether enlarged mediastinal nodes are seen ei-
ther on a standard posterior-anterior radiograph or
on a CT scan; these clinically positive nodes are also
known as clinical N2 disease. Patients with such
nodes who undergo surgical resection and postop-
erative adjuvant treatment have a five-year survival
rate of only 5 percent, as compared with patients
B
whose lymph nodes are positive but not enlarged
(five-year survival rate, 20 to 30 percent).17,18 Other
poor prognostic variables include the involvement
of nodes at multiple sites and extracapsular growth
of tumor in the lymph node.
Clinically, this patients disease was N0 because
no enlarged nodes were seen on routine radio-
graphs. Because the intraoperative frozen section
showed a positive node, I thought she might bene-
fit from preoperative chemoradiotherapy, so I elect-
ed not to proceed with the planned thoracotomy. Figure 2. Lymph-Node Biopsy Specimen (Hematoxylin
and Eosin).
pathological discussion There are nests of carcinoma cells (Panel A) adjacent to
fibrotic tissue. At higher magnification the cells are large,
Dr. Eugene J. Mark: The right paratracheal lymph- with no glandular or squamous differentiation (Panel B).
node specimen from mediastinoscopy was submit-
ted for analysis; it consisted mostly of metastatic
large-cell carcinoma (Fig. 2A). The cells had large,
pleomorphic nuclei, and several cells had very large Table 1. Standard Histologic Classification of Lung
nucleoli with clumped chromatin and prominent Cancer and Its Variants.
nucleoli. There was no gland formation or keratini-
Squamous-cell carcinoma
zation to indicate adenocarcinoma or squamous- Papillary
cell carcinoma (Fig. 2B). The subcarinal node did Small-cell
not contain tumor cells. Basaloid
Adenocarcinoma
The standard histologic classification of the com- Acinar
mon carcinomas of the lung is shown in Table 1. Papillary
This patient had an undifferentiated large-cell carci- Bronchioloalveolar
Solid with mucus
noma. The role of the pathologist in the evaluation
Large-cell carcinoma
of carcinomas of the lung is given in Table 2.19-21 Neuroendocrine
The histologic type should conform to the standard Clear-cell
classification. The grade is often given but has not Lymphoepithelial
Rhabdoid
proved to be an independent factor in prognosis.
Small-cell carcinoma
The most important issue is the staging, which in-
cludes an assessment of the size of the tumor, the
relationship of the tumor to the pleura, the pres-
ence or absence of lymph-node metastases, and the a metastasis (Table 3). The most commonly used
adequacy of resection margins, particularly at the markers are thyroid transcription factor 22,23 and
bronchus. cytokeratins of various molecular weights. Thyroid
Immunopathological markers are sometimes transcription factor is largely restricted to lung and
useful in distinguishing a primary lung cancer from thyroid cancer. The expression of cytokeratins of

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 case records of the massachusetts general hospital

Table 2. Pathological Considerations in the Diagnosis Table 3. Immunopathological Markers of Cancer.

of Lung Cancer.
Marker Expression
Histologic classification
Keratin (broad spectrum) All carcinomas
Histologic grade (optional)
Stage of tumor Carcinoembryonic antigen Adenocarcinoma
Size of primary tumor Keratins 7 and 20 Lung cancer (positive for keratin 7);
Extent of pleural invasion gastrointestinal cancer (positive
Status of lymph nodes for keratin 20)
Status of resection margins
Thyroid transcription factor 1 Lung and thyroid cancers
Investigational variables
Cellular reaction Calretinin and WT-1 Mesothelioma
Blood-vessel or lymphatic invasion CA 19-9 Pancreatic cancer
Effects of therapy Estrogen and progesterone receptors Breast cancer
Prostate-specific antigen Prostate cancer
Neuroendocrine markers (neuron- Small-cell carcinoma
various molecular weights in tumors mirrors that of specific enolase, synaptophysin,
the normal epithelium that the tumor arises from chromogranin)
or differentiates toward, and is useful in the diag-
nosis of metastases from the gastrointestinal tract
as well as the distinction of carcinomas of the lung these patients the disease can be cured by surgery,
from diffuse malignant mesothelioma. but the majority die from metastatic cancer. Strate-
gies that incorporate systemic chemotherapy offer
discussion of management the best chance of controlling distant metastatic
disease in both clinical N2 and minimal N2 lung
Dr. Lynch: In summary, this 56-year-old woman has cancer. A key question that we faced in the manage-
nonsmall-cell lung cancer, with clinical stage N0 ment of this case was how to optimally incorporate
or N1 disease and pathological stage N2 disease systemic chemotherapy and radiotherapy into her
a combination that is sometimes called minimal N2 treatment: Should they be given after surgery (adju-
disease. What is the optimal approach to care for vant) or before surgery (neoadjuvant)?
this patient? Before 2003, the role of adjuvant chemotherapy
Treatment of stage IIIA nonsmall-cell lung for completely resected lung cancer, with or with-
cancer is one of the most controversial topics in the out positive lymph nodes, was unclear. Four years
management of lung cancer. The most important ago, when treatment decisions for this patient were
initial distinction is to classify the disease as either being made, the data available did not support its
clinical N2 or clinical N1 or N0. Currently, oncolo- use. A 1995 meta-analysis found that cisplatin-
gists use the presence of lymph nodes on CT scans based adjuvant chemotherapy was associated with
or chest radiographs as the criterion for clinical N2 a 5 percent improvement in overall survival, but the
disease. A question for the near future is whether number of patients treated was too small to allow
PET scanning will change the preoperative staging an assessment of statistical significance.26 A study
classification. I suspect that patients whose disease in which the combination of cisplatin, etoposide,
is considered positive on the basis of PET scanning and radiotherapy was compared to radiotherapy
and negative on the basis of CT scanning will have alone after complete resection of stage II or III non
a prognosis that is somewhere between that of pa- small-cell lung cancer27 failed to show a benefit
tients with clinical N2 disease and minimal N2 dis- from adjuvant chemoradiotherapy.
ease. The increasing use of simultaneously regis- In 2003 and 2004, the results of two larger trials
tered PET and CT may make this distinction more were reported. One trial found that three cycles of
clear.24 platinum-based chemotherapy resulted in a 2 to
For patients with clinical N2 disease, there is 3 percent rate of absolute improvement in overall
wide agreement that surgery alone does not provide survival as compared with surgery alone, a finding
an acceptable cure rate.25 For patients with clinical that did not reach statistical significance; however,
N0 or N1 disease who have pathologically involved the number of patients in this study was not large
N2 nodes, also known as minimal N2 disease, there enough to permit detection of a 5 percent differ-
are several reasonable options. In nearly a third of ence in survival.28 The second trial was the largest

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 The new england journal
randomized trial reported to date for patients with
resected lung cancer.29 In this study, more than
1800 patients with stage I, II, or IIIA lung cancer
were randomly assigned after surgery to either ob-
servation or to one of four cisplatin-based chemo-
therapy regimens. At five years, the overall survival
was 44.5 percent in the group that received adju-
vant chemotherapy as compared with 40.0 percent
in the group that did not get adjuvant treatment
a statistically significant difference. This trial was
large enough to demonstrate a benefit of the mag-
nitude that is clinically meaningful to patients.
Thus, for this patient with minimal N2 disease,
surgical resection followed by three or four cycles of
adjuvant cisplatin-based chemotherapy would be a
reasonable treatment option. Had these data been
available when this patient presented, she would
have considered this option.
Trials of neoadjuvant therapy followed by surgery
for stage IIIA nonsmall-cell lung cancer have in-
volved both chemotherapy and combined chemo-
therapy and radiotherapy strategies. Phase 2 stud-
ies of chemotherapy followed by surgery (and often
postoperative radiotherapy) have reported cure rates
of between 15 percent and 20 percent.30,31 This
compares favorably with the 5 percent to 9 percent
survival rate reported for patients with clinical N2
cancer who were treated with surgery alone. How-
ever, the comparison is not completely fair, since pa-
tient selection could result in differences in known
prognostic factors. Two small, randomized trials re-
ported in the early 1990s32,33 showed a clear bene-
fit associated with chemotherapy followed by sur-
gery as compared with surgery alone; however, both
studies included patients with T3N0 disease, which
probably has biologic features and a pattern of re-
currence that differ from those of N2 disease. A
larger, randomized trial34 showed a trend toward
improved outcomes with chemotherapy as com-
pared with surgery alone, but the difference did not
reach statistical significance because of the small
number of patients in the study.
Dr. Choi will discuss the use of combined che-
motherapy and radiotherapy followed by surgery for
stage IIIA nonsmall-cell lung cancer.
Dr. Noah C. Choi: Important questions in planning
the appropriate multimodality therapy for a patient
such as this with stage IIIA (N2) nonsmall-cell
lung cancer include the following: What is the role
of radiotherapy relative to chemotherapy in down-
staging the tumor so that it can be resected? What
is the proper sequence for the use of radiotherapy
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of medicine
among the other treatments? How can toxic effects
from radiation be minimized?
A randomized, phase 3 clinical trial published
in abstract form in the early 1990s compared pre-
operative chemotherapy plus radiotherapy with che-
motherapy alone in patients with stage IIIA (N2)
and IIIB (T4) nonsmall-cell lung cancer.35 The
response rate, resection rate, and rate of freedom
from progression for preoperative, concurrent che-
moradiotherapy as compared with chemotherapy
alone were 67 percent versus 44 percent, 52 percent
versus 31 percent, and 40 percent versus 21 percent,
respectively; all the differences were statistically sig-
nificant. My colleagues and I conducted a phase 2
study in which 42 patients with stage IIIA (N2) non
small-cell lung cancer were treated with two courses
of preoperative cisplatin, vinblastine, and fluo-
rouracil, with concurrent radiation given in two
fractions per day, followed by surgery and another
course of postoperative chemoradiotherapy.36 The
tumor could be resected with negative margins in
81 percent of the patients. The overall survival rates
were 66 percent, 37 percent, and 37 percent at two,
three, and five years, respectively. Pathological ex-
amination of the surgical specimen showed down-
staging of the tumor in 67 percent of the cases. The
degree of tumor down-staging translated into a sur-
vival benefit: five-year survival rates after surgery
were 79 percent, 42 percent, and 18 percent for post-
operative tumor stages 0 (T0N0) and I (N0), stage
II (N1), and stage IIIA (N2), respectively. The South-
west Oncology Group, in another phase 2 study,
used a regimen of cisplatin and etoposide given
concurrently with 45 Gy of radiation, followed by
surgical resection. The five-year survival rate among
patients with stage IIIA (N2) disease was 35 per-
cent.37
Thus, the combination of chemotherapy and ra-
diotherapy has the potential advantage of enhanc-
ing local control while delivering drug doses that
can affect distant metastatic spread. Randomized
trials of chemotherapy compared with chemora-
diotherapy are needed to determine which strategy
is better before surgical resection.
The targeting of radiotherapy has improved
during the past 30 years, with the advent of three-
dimensional conformal radiation, intensity-modu-
lated radiation, and proton-beam radiation. These
techniques permit the delivery of radiation to the
tumor with normal tissue spared, and they allow
the delivery of radiation concurrently with chemo-
therapy without undue toxic effects.38,39 At the time
august 19 , 2004
 case records of the massachusetts general hospital

this patients care was planned, these techniques

were not standard, and she was treated with a two- A
dimensional technique.
Dr. Lynch: Finally, we need to consider whether
surgery is needed after chemotherapy or chemo-
radiotherapy. In a recent multicenter study, patients
with histologically proven N2 disease were random-
ly assigned to either induction chemoradiotherapy
(cisplatin, etoposide, and 45 Gy of radiation) fol-
lowed by surgery or to chemoradiotherapy alone.40
The initial data indicate that induction chemoradio-
therapy followed by surgery was superior in terms of
the time to progression and the rate of survival at B
five years (38 percent vs. 33 percent). However, the
trial was small and this difference, though potential-
ly clinically meaningful, was not statistically signif-
icant. Both neoadjuvant chemoradiotherapy and
chemoradiotherapy alone offer results that are supe-
rior to those of surgery alone for clinical N2 disease.
In the case under discussion, the decision was
made to administer neoadjuvant chemoradiother-
apy followed by surgery. Today, this strategy might
well still be the treatment of choice, but it would
Figure 3. Specimen of Resected Lung after Chemoradio-
certainly be reasonable to offer treatment with de-
therapy (Hematoxylin and Eosin).
finitive chemoradiotherapy without surgery or to op-
There is necrotic tumor containing cholesterol clefts
erate initially and follow up with adjuvant chemo- (Panel A) adjacent to desmoplastic inflammation and fi-
therapy. brosis. There is emphysema (Panel B) with free-floating
Dr. Temel: Therapy was begun with concurrent fragments of alveolar walls.
chemotherapy and radiation to the tumor region in
the right lung. She was treated with 45 Gy of radia-
tion to the right lung and hilus and the right para- response on radiography, because there can still
tracheal region in 25 fractions over a period of six be microscopic residual disease in either the lymph
weeks. She also received carboplatin at a dose calcu- nodes or lung. Close attention is given to the bron-
lated to result in an area under the concentration chial stump after induction therapy, and it is covered
time curve of 6.0 mg per milliliter per minute in a with a vascularized flap to prevent development of
three-week cycle and paclitaxel at a dose of 50 mg a bronchopleural fistula.
per square meter of body-surface area each week. The surgeon will do a complete mediastinal lym-
The patient had mild nausea, which was well con- phadenectomy, both for therapeutic reasons (to re-
trolled with ondansetron. She had mild esophageal move any residual cancer in the lymph nodes) and
mucositis and alopecia. Restaging studies showed a for restaging. It is preferable not to perform a right
decrease in the size of the mass in the right upper pneumonectomy in patients who have received
lobe from 2.5 cm to 2.0 cm and no evidence of met- induction therapy, because of the possibility of
astatic disease. higher-than-expected postoperative mortality. Pa-
Dr. Wright: After the induction therapy, both tients whose tumors can be removed either by lobec-
pulmonary-function studies and laboratory studies tomy or by left-sided pneumonectomy have a peri-
should be performed to make sure that there is a operative mortality rate similar to that of patients
good functional as well as a hematologic recovery, who have not received preoperative therapy.
which will enable the patient to tolerate surgery. Twelve weeks after this patients initial medias-
Because it usually causes hilar fibrosis, induction tinoscopy, I performed a right thoracotomy, with a
chemoradiotherapy often increases the difficulty of right upper lobectomy and mediastinal lymphade-
subsequent surgery. The surgeon treats the original nectomy.
volume of disease even if there has been a complete Dr. Mark: The lung resected after radiotherapy

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 The new england journal of medicine

and chemotherapy contained necrotic tumor; no
definitely viable cells remained and there was only
a single focus of possibly viable cells. Cholesterol
clefts and necrosis were surrounded by inflamma-
tion and fibrosis (Fig. 3A). Blood vessels were in-
flamed with intimal fibrosis, which could have been
caused by the cancer itself, by the radiation, or in
this case, by both. Free-floating fragments of alve-
olar walls in the parenchyma apart from the tumor
indicated there was emphysema as a consequence
of the patients smoking (Fig. 3B). The lymph-node
dissection specimens (paratracheal and subcarinal)
had no evidence of cancer cells.
Dr. Temel: Two months after the operation, the
patient received two additional cycles of full-dose
carboplatin and paclitaxel. Forty-two months after
the completion of therapy, she had no evidence of
recurrent disease.
Dr. Lynch: This patients case illustrates the need
for multidisciplinary management of nonsmall-
cell lung cancer. Although this patient was doing
well 42 months after the diagnosis, overall survival
in this disease is still poor, and novel approaches
need to be studied. Future trials in locally advanced
nonsmall-cell lung cancer will incorporate new
molecular agents. A key issue will be the identifica-
tion of patients who are likely to benefit from bio-
logic therapy. An example is the recent demonstra-
tion that activating mutations in the epidermal
growth factor receptor predict responses of non
small-cell lung cancers to the tyrosine kinase inhib-
itor, gefitinib.41 Ultimately, a successful care plan
for a patient with stage IIIA nonsmall-cell lung
cancer will need to include maximal local treat-
ment with surgery, radiotherapy, or both in addition
to systemic treatment that targets residual micro-
scopic tumor.
anatomical diagnosis
Large-cell undifferentiated carcinoma of the lung,
stage IIIA (T1N2M0).

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