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Cytological characteristics of pulmonary large cell neuroendocrine
carcinoma.Lung
Cancer. 2005 Jun;48(3):331-7. Epub 2005 Apr 7.
To establish
cytological features of pulmonary large cell neuroendocrine carcinoma
(LCNEC), we evaluated the cytological characteristics of LCNEC.
Samples from 25 histologically confirmed LCNECs (14 touch imprint (TI)
and 11 curettage) were analyzed. The findings were compared with those
for seven small cell lung carcinomas. Cytological findings of TIs were
as follows: Tumor cells were medium- to large-sized, round or
polygonal, and nuclear polymorphism was observed. Some of the tumor
cells had clearly identified cytoplasms, but naked nuclei were
frequently observed. Nuclei were round, oval, or polygonal, and
possessed thin and smooth nuclear membranes. The nuclear chromatin
pattern was finely or coarsely granular. One or two nucleoli were
observed in the nuclei, but were inconspicuous in some cases. Tumor
cells appeared in clusters, and rosette formation was observed, but
single cells were frequently observed also. Necrotic background and
nuclear streaking were frequently observed. In brush or curettage
specimens, the number of cells observed on a glass was small, but the
findings were almost the same as those for the TI samples. TI samples
have characteristic features, such as a neuroendocrine morphologic
pattern, large cell size, abundant cytoplasm, finely or coarsely
granular chromatin of the nucleus, and prominent nucleoli, and the
diagnosis of LCNEC is possible. In brush or curettage specimen, the
LCNEC diagnosis may be possible if a sufficient number of tumor cells
are obtained.
Imprint cytologic features of pulmonary large cell neuroendocrine
carcinoma: Comparison with classic large cell carcinoma.Oncol
Rep. 2004 Feb;11(2):285-8
The World Health
Organization (WHO) categorized large cell neuroendocrine carcinoma (LCNEC)
as a variant of large cell carcinoma in 1999. However, cytologic
features of these tumors have not yet been adequately characterized.
The cytologic features of 24 cases of LCNEC were analyzed and compared
to the features of 16 cases of classic large cell carcinoma (CLCC).
Giant cells, neutrophils and cytophagocytosis were observed more
frequently in CLCC than in LCNEC (p<0.05), whereas the unclear border
of tumor cells was seen more frequently in LCNEC (p<0.05). The
presence of nuclear atypia, such as anisokaryosis, nuclear budding,
irregularity of nuclear margins, and multinucleation (having three or
more nuclei), was observed less frequently in LCNEC. Characteristic
arrangements of tumor cells, such as rosette formation, and palisading,
were observed only in LCNEC cases. In morphometric studies, the
nuclear areas, cytoplasmic areas, and nuclear rotundity ratios were
significantly higher in CLCC cells than in LCNEC cells (p<0.05).
However, N/C ratios were significantly higher in LCNEC than in CLCC.
LCNEC cells have less nuclear atypia than CLCC cells, and have the
characteristic arrangements of tumor cells, such as palisading and
rosette. It is possible to preoperatively differentiate LCNEC from
CLCC by careful cytologic characterization.
Diagnostic findings
of bronchial brush cytology for pulmonary large cell neuroendocrine
carcinomas: comparison with poorly differentiated adenocarcinomas,
squamous cell carcinomas, and small cell carcinomas.Cancer.
2003 Aug 25;99(4):247-54.
BACKGROUND:
Large cell neuroendocrine carcinoma (LCNEC) of the lung has been
proposed as a new disease entity. To establish diagnostic features,
bronchial brush cytologic findings were evaluated. METHODS: Bronchial
brush cytology material of 20 LCNECs was evaluated by light microscopy
and stained immunocytochemically with protein gene product 9.5
(PGP9.5), neuron-specific enolase, and neural cell adhesion molecule
antibodies. The findings were compared with those for 19 poorly
differentiated adenocarcinomas (ACs), 18 poorly differentiated
squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs).
RESULTS: Frequently observed characteristic cytologic findings of
LCNECs were necrotic background (90.0%), large tumor cell size
(90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei
in all LCNECs showed a fine granular chromatin pattern and possessed
one or a few nucleoli. Indian-filing and rosette arrangements were
observed in less than one-half of the LCNECs. In poorly differentiated
ACs and SCCs, these features were less frequent, whereas thick nuclear
membranes were observed more often. In SCLCs, tumor cell adhesions and
Indian-filing or nuclear molding were observed more frequently than in
LCNECs, whereas a necrotic background, tumor cell clusters, large
tumor cells, and nucleoli were less prominent. The majority of LCNECs
(80.0%) had a positive immunocytochemical reaction for PGP9.5, in
contrast to the low positive reactions for ACs (42.1%) and SCCs
(30.8%). CONCLUSIONS: Large cell neuroendocrine carcinomas can be
diagnosed preoperatively by bronchial brush cytology using reliable
parameters, including tumor cell size, naked nuclei, thin nuclear
membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic
background.
Large-cell
neuroendocrine carcinoma of the lung: proposed criteria for cytologic
diagnosis.Diagn
Cytopathol. 2001 Jan;24(1):58-64.
The category of
large-cell neuroendocrine carcinoma (LCNEC) of the lung, proposed to
expand the traditional scheme of typical carcinoid, atypical carcinoid
(AC), and small-cell carcinoma (SCC), based on histologic features,
has not been defined in cytology. We attempt to describe LCNEC
cytologically. Cytologic features in 16 histologically confirmed
LCNECs in fine-needle aspiration biopsies, cell blocks, bronchial
brushes, washes, and sputum specimens stained with Diff-Quik,
Papanicolaou, hematoxylin-eosin, chromogranin, and synaptophysin were
analyzed. Three poorly differentiated nonsmall-cell carcinomas, 4 SCCs,
and 2 atypical carcinoids were studied similarly. Twenty specimens
from 16 histologically confirmed cases of LCNEC with original
cytologic diagnoses including high-grade neuroendocrine carcinoma,
large-cell carcinoma, nonsmall-cell carcinoma, poorly differentiated
carcinoma, adenocarcinoma, and SCC, were examined. Features included
flattened three-dimensional clusters with peripheral palisading,
moderate to large single cells with scant (alcohol-fixed) or moderate
(air-dried) cytoplasm; and large, oval, or polygonal nuclei with
irregular contours, thickened nuclear membranes, and finely or
coarsely granular chromatin, showing some molding and crush artifact.
Nucleoli were generally present, and occasionally prominent. Mitosis
and necrosis were apparent. Neuroendocrine stains were applied to all
specimens, with at least one marker, commonly synaptophysin, positive
in 18/20 specimens. LCNEC can be diagnosed in cytologic material,
using morphology confirmed by immunocytochemistry. Treatment can be
offered on the basis of cytologic examination.
Clinical characterization of pulmonary large cell neuroendocrine
carcinoma and large cell carcinoma with neuroendocrine morphology.Cancer.
2001 Jun 1;91(11):1992-2000.
BACKGROUND: Large
cell carcinoma has been classified as four potential types based on
its neuroendocrine morphology and evidence of neuroendocrine
differentiation discernible by immunohistochemistry or electron
microscopy. However, the clinical relation among these four categories
has not been clearly defined. In 1999, the World Health Organization
(WHO) categorized large cell neuroendocrine carcinoma as a variant of
large cell carcinoma. MATERIAL AND METHODS The authors analyzed 119
cases of large cell carcinoma from a total of 2070 primary lung
carcinoma cases resected surgically between 1969-1999. Using light
microscopy, electron microscopy, and immunohistochemical staining, the
authors reclassified these cases into large cell neuroendocrine
carcinoma (LCNEC), large cell carcinoma with neuroendocrine
differentiation (LCCND), large cell carcinoma with neuroendocrine
morphology (LCCNM), and classic large cell carcinoma (CLCC). RESULTS:
In multivariate analyses, the authors found that large cell carcinoma
with neuroendocrine features, which combined LCNEC, LCCND, and LCCNM,
impacted both the overall survival and disease-free survival of
patients. The clinical behavior of LCCNM was similar to that of LCNEC.
CONCLUSIONS: Large cell carcinomas with neuroendocrine features appear
to be more clinically aggressive than CLCCs. The authors' findings
suggest that the histologic identification of neuroendocrine features
in tumor tissue from patients diagnosed with large cell carcinoma of
the lung may have clinical relevance.
Large cell neuroendocrine carcinoma of the
lung: a comparison with large cell carcinoma with neuroendocrine
morphology and small cell carcinoma.Lung
Cancer. 2005 Feb;47(2):225-33.
Large cell
neuroendocrine carcinoma (LCNEC) of the lung is a malignant
neuroendocrine tumor clinicopathologically similar to and falling
in-between atypical carcinoid tumor and small cell lung carcinoma
(SCLC). The diagnosis of LCNEC is based mainly on a characteristic
neuroendocrine morphology and biological neuroendocrine
differentiation. In order to know the discrepancy between
morphological and biological neuroendocrine differentiation, LCNEC was
immunohistochemically and molecular biologically compared with large
cell carcinoma with neuroendocrine morphology (LCCNM), which lacked
only biological neuroendocrine differentiation among the criteria of
LCNEC. Immunohistochemically, disruption of the RB pathway, namely a
lack of RB expression and simultaneous overexpression of p16 protein,
was characteristic of LCNEC, but not LCCNM. In G2/M cell cycle
regulation, 14-3-3 sigma expression was markedly reduced in LCNEC.
Moreover, the antibody 34 beta E12 recognizing a set of large-sized
keratin gave a different staining pattern between LCNEC and LCCNM. The
immunohistochemical data suggested that LCNEC has a similar biological
marker profile to SCLC and different from LCCNM. However, a loss of
heterozygosity (LOH) analysis using microsatellite markers showed a
high frequency of LOH at 3p in both LCNEC and LCCNM as well as in
SCLC. Morphological neuroendocrine differentiation might not be
identical to biological neuroendocrine differentiation in large cell
carcinoma of the lung.
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