European Journal of Cardio-Thoracic Surgery, Vol 12, 698-702, Copyright © 1997 by European Association for Cardio-thoracic Surgery
Results after surgery in undifferentiated large cell carcinoma of the lung: the role of neuroendocrine expression
H Wertzel, PR Grahmann, S Bansbach, W Lange, J Hasse and N Bohm
Department of Thoracic Surgery, University Hospital of Freiburg, Germany. Wertzel@chll.ukl.uni-Freiburg.de
OBJECTIVE: The objective of this study was to define the incidence of light
microscopically undifferentiated large cell carcinomas, to analyze tumor
stages, types of resections necessary and postsurgical survival.
Additionally we tried to evaluate whether or not neuroendocrine expression
influences the biological behavior of these tumors. METHODS: Light
microscopic specimens of 105 patients having undergone surgery for
undifferentiated large cell carcinoma were reviewed following the 1981 WHO
criteria. Fifty eight cases were excluded because elements of adeno- or
squamous cell carcinoma, neuroendocrine or combined patterns of
histological differentiation were observed. The remaining 47 cases of pure
undifferentiated large cell carcinoma were evaluated immunohistochemically
for neuroendocrine differentiation using a combination of the markers
neuron specific enolase, synaptophysin and chromogranin A. The hospital
charts of the patients were analyzed retrospectively recording tumor stage,
operative procedure, postoperative complications, postoperative adjuvant
treatment procedures, actual tumor state and survival time. RESULTS:
Thirteen patients (27.7%) had postsurgical tumor stage I, 5 (10.6%) stage
II, 15 (31.9%) stage IIIA, 9 (19.1%) stage IIIB, and 5 (10.6%) stage IV. In
46 of 47 patients resections of lung parenchyma were performed (wedge
resection n = 5, segmental resection n = 1, lobectomy n = 27, bilobectomy n
= 3, pneumonectomy n = 10), in 6 patients combined with broncho- and/or
angioplastic procedures. At the time of chart review 20 (42.5%) patients
were still alive. The cause of death in the remaining patients was
recurrent lung cancer in the majority of cases (24 or 92.30%). The overall
mean survival of the 46 patients undergoing parenchymal resections was 19
months, the 3-year survival rate 31.7%. The immunohistochemical examination
demonstrated expression of neuron specific enolase in 15 cases.
Synaptophysin and chromogranin A were not detected in any case. For these
15 patients the mean survival was 25.6 months (+/- 4.3) and the 1-year
survival rate 67% (confidence interval 43-91%) compared to 13.8 (+/- 2.1)
months and 33.5% (confidence interval 15.3-51.7%) in the remainder. The
difference was not significant (P = 0.06). CONCLUSIONS: The light
microscopic diagnosis of undifferentiated large cell carcinoma revealed to
be subject to considerable interobserver variability. Undifferentiated
large cell carcinoma takes a more unfavorable clinical course than other
non-small cell carcinomas. Despite lack of statistical significance,
expression of neuron specific enolase appeared to be associated with less
aggressive biological behavior of the respective neoplasms.
Immunohistochemical evaluation of undifferentiated large cell carcinomas
using a combination of neuron specific enolase, chromogranin A, and
synaptophysin did not provide more therapeutically relevant information
than that obtained by light microscopic assessment.
