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Large-cell neuroendocrine carcinoma of the lung.Cancer
Control. 2006 Oct;13(4):270-5.
BACKGROUND:
Large-cell neuroendocrine carcinoma (LCNEC) of the lung displays
morphologic and immunohistochemical characteristics common to
neuroendocrine tumors and morphologic features of large-cell
carcinomas. Because surgical resection of LCNEC in many series has
been described with 5-year actuarial survival that is far worse than
that reported for other histologic variants of non-small-cell lung
cancer (NSCLC), considerable debate has emerged as to whether these
tumors should be classified and treated as NSCLC or small-cell lung
cancer. METHODS: The initial evaluation and diagnosis, tumor
classification, surgical treatment, results of therapy, and long-term
prognosis of patients with LCNEC based on our experience are
discussed, and a review of the literature is presented. RESULTS:
Patients with LCNEC are more likely to develop recurrent lung cancer
and have shorter actuarial survival than patients with other
histologic types of NSCLC, even in those with stage I disease.
CONCLUSIONS: Accurate differentiation of LCNEC from other types of
NSCLC is important because it identifies those patients at highest
risk for developing recurrent disease. Efforts to identify effective
adjuvant therapies are needed to improve treatment outcomes with this
aggressive type of lung cancer.
Large
cell neuroendocrine carcinoma: an aggressive form of non-small cell
lung cancer.J
Thorac Cardiovasc Surg. 2005
Jul;130(1):166-72.
OBJECTIVE:
Large cell neuroendocrine carcinomas of the lung display morphologic
and immunohistochemical characteristics common to neuroendocrine
tumors and the morphologic features of large cell carcinomas. Surgical
resection of large cell neuroendocrine carcinomas in many series has
been described, with 5-year actuarial survivals ranging from 13% to
57%. Considerable debate has emerged as to whether these tumors should
be classified and treated as non-small cell lung cancers or small cell
lung cancers. The objective of this study was to report the outcome of
surgical resection in patients with large cell neuroendocrine
carcinomas. METHODS: An analysis of our tumor registry was performed
to identify all patients undergoing surgical resection of lung cancer
between July 1, 1988, and December 31, 2002, for large cell tumors.
Cases were then segregated into large cell neuroendocrine carcinomas,
mixed large cell neuroendocrine carcinomas (in which at least one
portion of the tumor was a large cell neuroendocrine carcinoma), or
large cell carcinomas on the basis of morphology and differentiation.
Follow-up was complete on all patients, with a mean follow-up of 48
months. Type of resection, mortality, and survival by stage were
analyzed. Kaplan-Meier survival was determined for all patients from
the date of surgical intervention. Cox proportional hazards model
analysis incorporating the variables of age, sex, histology, and stage
estimated the effect of large cell neuroendocrine carcinomas and mixed
large cell neuroendocrine carcinomas on recurrence and death. The
stage of disease in all patients was assessed according to the 1997
American Joint Committee on Cancer guidelines. RESULTS: Of the 2099
patients who underwent resection, 82 (3.9%) had large cell lung
cancers. Perioperative mortality was 2.4%. Overall survival and
freedom from recurrence at 5 years for the entire group was 47.1% and
58.4%, respectively. Overall survival by histologic subtype at 5 years
was 30.2% for patients with large cell neuroendocrine carcinomas (n =
45), 30.3% for patients with mixed large cell neuroendocrine
carcinomas (n = 11), and 71.3% for patients with large cell carcinomas
(n = 21). Survival was significantly worse for patients with large
cell neuroendocrine carcinomas than for patients with large cell
carcinomas ( P = .013). The presence of large cell neuroendocrine
carcinomas in the specimen (the large cell neuroendocrine carcinoma
and mixed large cell neuroendocrine carcinoma groups combined) was
significantly associated with decreased survival (relative risk, 2.44;
95% confidence interval 1.29-4.58; P = .003) and decreased freedom
from recurrence (relative risk, 4.52; 95% confidence interval,
1.76-11.57; P < .001). CONCLUSION: Patients with large cell
neuroendocrine carcinomas have a significantly worse survival after
resection than patients with large cell carcinomas, even in stage I
disease. Accurate differentiation of large cell neuroendocrine
carcinoma from large cell carcinoma is important because it identifies
those patients at highest risk for the development of recurrent lung
cancer.
Large cell
neuroendocrine carcinoma and large cell carcinomas with neuroendocrine
morphology of the lung: prognosis after complete resection and
systematic nodal dissection.Ann
Thorac Surg. 2003 Feb;75(2):348-52.
BACKGROUND:
Large cell neuroendocrine carcinoma (LCNEC) and large cell carcinoma
with neuroendocrine morphology of the lung are both currently
classified as subtypes of large cell carcinomas according to the World
Health Organization IASLC classification system for lung and pleural
tumors. Prognosis is reported as similar to that of small cell
carcinomas. There is no consensus on management of this subset and
adjuvant chemotherapy is recommended by some for early stage LCNEC to
impact long-term prognosis. We retrospectively reviewed a cohort of
patients at our institution who had this type of tumor to determine
factors that might influence survival. METHODS: Twenty-one cases of
LCNEC and large cell carcinoma with neuroendocrine morphology were
identified in the files of the Royal Brompton Hospital between 1986
and 1999. All patient data were reviewed, and complete follow-up was
achieved with 20 of these patients. RESULTS: Of the 21 patients
identified, 20 underwent resection with systematic nodal dissection in
18. There was no in-hospital mortality. Of those patients fully staged
by systematic nodal dissection, 9 were stage I, 5 were stage II and 4
were stage III. Median follow-up was 25 months (range, 2 to 120
months). At the time of review, 11 patients were alive and free of
disease. One patient was alive and free of disease when lost to
follow-up. Nine patients had died, 7 related and 2 unrelated to
disease. The 5-year actuarial survival for the entire group was 47%.
The actuarial survival of accurately staged, stage I patients at 5
years was 88%. The actuarial survival of patients in stage II and III
was 28% at 5 years. CONCLUSIONS: LCNEC and large cell carcinoma with
neuroendocrine morphology are aggressive tumors, but patients with
completely resected disease after systematic nodal dissection have a
better prognosis than previously described. Patients with more
advanced disease have a poor prognosis.
Large cell
neuroendocrine carcinoma of the lung: a clinicopathologic study of
eighty-seven cases.J
Thorac Cardiovasc Surg. 2002 Aug;124 (2):
285-92.
OBJECTIVE:
Large cell neuroendocrine carcinoma of the lung is a newly recognized
clinicopathologic entity. The clinical characteristics and optimal
treatment of patients with large cell carcinomas are not yet
established. The aim of this study was to define the clinicopathologic
characteristics of large cell neuroendocrine carcinoma. METHODS: The
histologic characteristics of the patients receiving an initial
diagnosis of poorly differentiated non-small cell lung carcinoma (n =
484), small cell carcinoma (n = 55), carcinoid (n = 31), and large
cell neuroendocrine carcinoma (n = 12) were retrospectively reviewed
according to World Health Organization criteria. Immunohistochemistry
was performed to confirm the neuroendocrine phenotype. The outcomes
and other clinical characteristics of those patients with large cell
neuroendocrine carcinoma were retrospectively analyzed and compared
with those of patients with poorly differentiated carcinoma of other
histologic types. RESULTS: A total of 87 patients were given a
diagnosis of large cell neuroendocrine carcinoma after the histologic
review. These patients comprised 3.1% of all patients undergoing
resection for primary lung cancer during the same period. The overall
5-year survival was 57%. The 5-year survivals of patients with stage
I, II, III, and IV disease were 67%, 75%, 45%, and 0%, respectively.
There was no statistically significant difference between the overall
survival of patients with large cell neuroendocrine carcinoma and
those with other non-small cell lung cancers. There was a significant
difference between the survival of patients with stage I large cell
neuroendocrine carcinoma and that of patients with the same stage of
other non-small cell lung carcinomas. The site of the first documented
recurrence was locoregional in 12 patients (34%), distant metastases
in 20 patients (57%), and both simultaneously in 3 patients.
Locoregional lymph node recurrences were observed frequently. More
than 80% of recurrences were found within 1 year after the operation.
CONCLUSION: In terms of prognosis, large cell neuroendocrine carcinoma
is distinctly different from other non-small cell lung cancers. The
prognosis of large cell neuroendocrine carcinoma was poor, even for
early stage disease; the prognosis of the stage I disease of large
cell neuroendocrine carcinoma was poorer than that of the same stage
of other non-small cell lung cancers. Because of its aggressive
clinical behavior and poor prognosis, large cell neuroendocrine
carcinoma should be recognized as one of the poorest prognostic
subgroups among primary lung cancers, and therefore novel therapeutic
approaches should be established.
Large cell
neuroendocrine carcinoma of the lung: a histologic and
immunohistochemical study of 22 cases.Am
J Surg Pathol. 1998 May;22(5):526-37.
Large cell
neuroendocrine carcinoma (LCNEC) of the lung is defined as a poorly
differentiated and high-grade neuroendocrine tumor that is
morphologically and biologically between atypical carcinoid and small
cell lung carcinoma (SCLC). During a survey concerning bcl-2 protein
expression in the subtypes of lung cancer, we noticed that two
previously diagnosed non-SCLCs met the criteria for LCNEC. Because
LCNEC is a newly recognized clinicopathologic entity and because all
reported cases have been retrieved from the so-called "neuroendocrine
tumor file," we suspected that LCNEC had been underdiagnosed. In the
present study, we histologically reviewed 766 surgically resected lung
cancers and were able to diagnose 22 (2.87%) LCNECs with the
neuroendocrine features subsequently confirmed by immunostaining for
multiple neuroendocrine markers. Each case stained positively for at
least three general neuroendocrine markers, and 12 (54.5%) also were
positive for neuroendocrine hormones. Histologically, most LCNECs
showed a marked decrease in or a loss of organoid architecture and
could be mistaken for poorly differentiated adenocarcinoma or squamous
cell carcinoma. Because our LCNECs are the first to be identified by
retrospective review of routinely diagnosed lung cancers, and 18 had
been classified as non-SCLC, they may represent cases relatively
difficult to diagnose. The present study shows that the most difficult
diagnostic factor of LCNEC is the recognition of its light microscopic
neuroendocrine features, and LCNEC must be distinguished not only from
atypical carcinoid or SCLC, but also from common non-SCLC.
Histologically, when an organoid architecture is subtle or absent, the
rosettelike structure becomes the best marker for the recognition of
neuroendocrine differentiation. Clinically, the prognosis for our
LCNECs was significantly worse than that for stage-comparable non-SCLCs
(p = 0.046).
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