1. health and fitness
2. disease
3. cancer

The 7th Korea‐Japan Joint Meeting for
Diagnostic Cytopathology
November 3, 2007
November 1, 2008
Hotel Tirol, Muju Resort
The Korean Society for Cytopathology
The Japanese Society of Clinical Cytology
Support：The Korean Federation of Science
and Technology Societies
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CONTENTS
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Opening Address ·
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Special Lecture ·
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1. New ancillary techniques in fine needle aspiration :
Korean experience
Professor Tae Sook Hwang (Konkuk University Hospital)
2. New ancillary techniques in liquid based cytology:
Korean experience
Professor Ji Shin Lee (Chonnam National University Hwason Hospital)
3. Application of molecular technique on cytologic specimen;
Breast Cancer
Professor Shinobu Umemura (Tokai University School of Medicine)
4. Cytological characteristics and differentiation of small
adenocarcinoma of the lung
Professor Reiji Haba (University Hospital, Faculty of Medicine, Kagawa University)
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Part I ( 1 - 10)
Part II (11 - 21)
Chairpersons : Professor Kiyomi Taniyama,
Professor Chang Hun Lee
Chairpersons : Professor Tatsuo Sawada,
Professor Hye Kyung Lee
List of the Japanese Participants ·
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·62
Opening Address
Dear Colleagues,
0n behalf of the Korean Society for Cytopathology, it is my great pleasure to give a
welcome address 'The 7th Korea-Japan Joint Meeting for Cytopathology at Muju.
In recent years, a considerable expansion in the fields of cytologic diagnosis, especially
in liquid-based cytology, immunocytochemistry and cytogenetic analysis has been
achieved. At this meeting, the subject of "New ancillary test for cytopathology" will be
discussed. We can share the knowledge and experiences about new cytopathologic
technique.
Apart from joining academic program, you will experience staying at a deep and calm
high mountain resort, where is famous for its autumn beauty.
I sincerely welcome to all participants for attending this meeting again, and I'd like to
thank to the Japanese Society of Clinical Cytology for financial support for this meeting.
I wish all of you enjoy the Joint Meeting.
Thank you very much.
November 1, 2008
Chang Suk Kang, MD
President
The Korean Society for Cytopathology
- 1 -
The 7th Korea-Japan Joint Meeting for Diagnostic
Cytopathology
Saturday, November 01, 2008
Hotel Tirol B2 Grand Ballroom
Muju Resort, Korea
8:30 -
Registration(Hotel Tirol B2 Grand Ballroom)
8:50 - 9:00
Opening Address
Chang Suk Kang, President, The Korean Society for Cytopathology
Atsuhiko Sakamoto, Representative Japanese Society of Clinical
Cytology Committee for International Affairs
9:00 - 10:50
New ancillary techniques of Cytopathology in Korea and Japan
Chairpersons : Professor Mitsuyoshi Hirokawa
Professor Young Chae Chu
1. New ancillary techniques in fine needle aspiration : Korean experience
Professor Tae Sook Hwang (Konkuk University Hospital)
2. New ancillary techniques in liquid based cytology: Korean experience
Professor Ji Shin Lee, (Chonnam National University Hwason Hospital)
3. Application of molecular technique on cytologic specimen; Breast Cancer
Professor Shinobu Umemura, (Tokai University School of Medicine)
4. Cytological characteristics and differentiation of small adenocarcinoma of the lung
Professor Reiji Haba, (University Hospital, Faculty of Medicine, Kagawa University)
10:50 - 11:00
Photograph
11:00 - 11:20
Coffee Break(Lobby)
11:20 - 12:00
Poster discussion and closing(Lobby)
Chairpersons Part I ( 1- 10) : Professor
Professor
Part II (11 - 21) : Professor
Professor
12:30 - 14:00
Lunch
- 2 -
Kiyomi Taniyama
Chang Hun Lee
Tatsuo Sawada
Hye Kyung Lee
Special lecture
New ancillary techniques of Cytopathology
in Korea and Japan
Chairpersons : Professor Mitsuyoshi Hirokawa
Professor Young Chae Chu
1. New ancillary techniques in fine needle aspiration :
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Professor Tae Sook Hwang (Konkuk University Hospital)
2. New ancillary techniques in liquid based cytology:
Korean experience ·
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Professor Ji Shin Lee (Chonnam National University Hwason Hospital)
3. Application of molecular technique on cytologic specimen;
Breast Cancer ·
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Professor Shinobu Umemura (Tokai University School of Medicine)
4. Cytological characteristics and differentiation of small
adenocarcinoma of the lung ·
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·26
Professor Reiji Haba (University Hospital, Faculty of Medicine, Kagawa University)
Special lecture (1)
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Special lecture (2)
New ancillary techniques in liquid based cytology：
Korean experience
-Detection of Cervical Neoplasia by Promoter Hypermethylation Assay in
Liquid‐based Cytology SamplesJi Shin Lee
Department of Pathology Chonnam National University Medical School
Cytological screening using the Pap‐smear led to a remarkable reduction of the
mortality of cervical cancer. After several years of problems with poor rates of
sensitivity and unsatisfactory samples, the Pap test was improved with the introduction
of liquid‐based cytology (LBC) preparations and the potential use of residual material in
molecular investigation. There are many potential useful options to be considered for
molecular maker‐based assays, which can be summarized as follows: chromosomal
abnormalities; cell cycle check points; oncogene expression/function; tumor suppressor
gene expression; apoptotic markers; and epigenetic regulation such as methylation. The
aim of this review is to discuss the diagnostic feasibility of promoter hypermethylation
in gynecological cytology.
Introduction
Cancer of the uterine cervix is an important cause of death in women worldwide and
the forth most common malignancy in Korean women. In Korea and other developed
countries, the incidence and mortality rates of invasive cervical cancer have decreased
significantly since conventional cytology began to be used for cervical cancer screening.
However, identification of cervical neoplasia relying on microscopic examination of
exfoliated cervical cells is associated with many problems, including the low test
sensitivity.
LBC was introduced in the mid‐1990s to increase the sensitivity and specificity of
cervical screening. With this method, the smear sample is washed in a fluid and a
monolayer of cervical cells is spread on a slide. LBC reduced problems related to
sampling errors, poor sample preparation, and screening errors. LBC has greater
sensitivity compared with conventional Pap smears for the detection of cervical
squamous lesions and offers the advantage of providing residual sample that can be
- 19 -
used for ancillary testing, such as that for high‐risk human papilloma virus (Hr‐HPV)
DNA. Long term storage of LBC medium permits study of samples years after their
collection, with minor DNA/RNA damage. Nonetheless screening remains a labor‐
intensive complex method, the outcome of which depends on human judgment.
Therefore, more objective screening tests based on a specific biomarker which was only
expressed in dysplastic cervical epithelial cells but not in normal cervical cells, are still
needed.
Methylation
Cytosines are methylated in the human genome mostly when located 5' to a
guanosine. These CpG nucleotides have been severely depleted in the vertebrate genome
to about 20% of the predicted frequency and most CpG dinucleotides (over 70%) are
methylated. CpG dinucleotides also occur in transcribed portions of the genome,
clustered in regions termed CpG islands. CpG islands are typically 0.5‐kb long, and
located in the proximal promoter of more than half of all human genes. In normal cells,
most CpG islands are unmethylated and associated with active genes or genes capable
of active transcription. In tumors, many CpG islands exhibit aberrant hypermethylation
resulting in inappropriate transcriptional repression and gene inactivation.
Aberrant promoter hypermethylation is an early event in carcinogenesis and is often
present in the precursor lesions of various cancers. Aberrant promoter hypermethyatlion
specific to tumor cells can be used as a marker to detect tumor cells. As a marker to
detect tumor cells, DNA methylation has several advantages over mutations. First,
incidences of aberrant methylation of specific CpG islands are higher than those of
mutations. Secondly, aberrant promoter hypermethylation of a DNA molecule can be
sensitively detected, even when it is embedded in an excess amount of normal DNA
molecules, by methylation‐specific polymerase chain reaction (MSP) and quantitative
MSP (Q‐MSP). Thirdly, detection of aberrant promoter hypermethylation is technically
simple. Aberrant methylation usually takes place in an all‐or‐nothing manner, and it
can be detected using only one set of PCR primers. On the other hand, mutations can
take place in various regions of a gene, and many primer sets are necessary for
complete analysis.
Methods for methylation analysis
Conventional MSP is usual method to detect methylation status of promoter region of
cancer‐related genes. In MSP method, PCR primers are designed to be complementary
to completely methylated or completely unmethylated target DNA where methylated
and unmethylated primer sets differ only in the CpG position of the bisulfite converted
- 20 -
primary sequence: methylated primer sets contain CpG dinucleotides and unmethylated
primers contain TG at these positions. In the laboratory, this method has had a
tremendous
impact
on
the
efficiency
of
DNA methylation
analysis.
However,
conventional MSP is limited to a technique to detect cancer cells because scoring for
methylation based on visualization of bands can be subjective and not automated.
To address these issues at least in part, a quantitative assay has been developed. The
Q‐MSP assay provides several distinct advantages over conventional MSP: (a) omission
of all of the post‐amplification steps reduces the risk of contamination and increases the
throughput of the system; (b) the assay is more stringent and more specific because in
addition to the two PCR primers, the fluorescent‐labeled hybridization probe has to
anneal correctly between the two primers; (c) the assay is quantitative, automated, and
readily adaptable to clinical setting and screening studies; and (d) the assay is
amenable to multiplex amplification for the analysis of panels in clinical samples.
Fackler et al. developed quantitative multiplex MSP (QM‐MSP) method that allows
quantification of DNA methylation for a panel of genes (Fig. 1) and found out that it
accurately distinguished between benign and cancer cells in ductal fluid specimens. We
also found out QM‐MSP analysis of a key panel of genes may be useful as an ancillary
tool for DCIS detection in breast tissues (Fig. 2).
Fig. 1. Scheme for the quantitative multiplex methylation‐specific PCR.
Fig. 2. Promoter methylation levels of APC1, HIN‐1 and RASSF1A in 16 normal breast tissues
(NR), 10 usual ductal hyperplasia (UDH), and 48 ductal carcinoma in situ (DCIS).
Black bar represent median value for each gene.
- 21 -
Methylation study in cervical neoplasia
There are numerous reports demonstrating that tumor suppressor genes belonging to
nearly every cancer pathway or function category have silenced or diminished their
expression due to abnormal promoter hypermethylation in cervical carcinoma (Fig. 3).
Aberrant promoter hypermethylation of selective tumor suppressor genes has been
detected in squamous intraepithelial lesions (SIL) and invasive cervical cancer. The
frequency of hypermethylation increased significantly with increasing severity of
neoplasia present in the cervical biopsy. Similar promoter hypermethylation patterns
have been also seen in a panel of genes from exfoliated cervical cytology samples and
corresponding biopsy specimens.
The identification of novel genes or combination of genes that are methylated in high
SIL (HSIL) and invasive cervical cancer but not in negative/low SIL (LSIL) samples is
necessary to use of DNA methylation as a molecular marker for cervical cancer
screening. In the largest such study, Feng et al. studied 21 candidate hypermethylated
genes in 319 exfoliated cell samples using MSP and identified a panel of three (DAPK1,
RAR‐β, and TWIST1), which were sensitive and specific for invasive cervical cancer and
its immediate precursor cervical intraepithleial neoplasia 3 (CIN3). They estimated that
detection of hypermethylation of these three genes in exfoliated cell samples would
identify histologically confirmed CIN3 or worse with a sensitivity of 60% and a
specificity of 95%. Lai et al. recently evaluated methylation rates of all 6 genes (SOX1,
PAX1, LMX1A, NKX6‐1 and WT1) in normal, LSIL, HSIL and squamous cell carcinoma
(SCC). PAX1 conferred the best performance with sensitivities of 86% and specificities of
82% for SCC and with sensitivities of 54% and specificities of 99% for HSIL/SCC.
Fig. 3. View of cervical carcinogenesis from a methylation standpoint
- 22 -
Parallel testing of HPV and PAX1 methylation in cervical swabs confers an improved
sensitivity than HPV testing alone (80% vs. 66%) without compromising specificity (63%
vs. 64%) for HSIL/SCC.
The detection of DNA methylation in liquid‐based Pap tests by Q‐MSP allows for
quantitation of relative levels of methylation in samples and the establishment of an
appropriate cutoff value for a positive test. Very few studies investigated the use of Q‐
MSP as a diagnostic tool for cervical neoplasia using cervical scrapings. Using Q‐MSP,
Wisman et al. investigated promoter hypermethylation of 12 genes in cervical scrapings,
obtained from cervical cancer patients (SCC as well as adenocarcinomas) and controls.
CALCA, DAPK, ESR1, TIMP3, APC and RAR‐β promoters were significantly more often
hypermethylated in cancers than in controls. Combining 4 genes (CALCA, DAPK, ESR1
and APC) yielded a sensitivity of 89% (with all adenocarcinomas identified), equal to
cytomorphology (89%) and Hr‐HPV (90%). The 4‐gene Q‐MSP proved theoretically
superior to cytomorphology as well as Hr‐HPV in specificity (100% vs. 83 and 68%,
respectively). Kahn et al. recently analyzed the frequency and relative level of promoter
methylation for DAPK1, IGSF4, SPARC, and TFPI2 in biopsy‐confirmed HSIL and
LSIL, and negative residual liquid‐based Pap tests. They demonstrated that methylation
of each of the 4 genes occurs more frequently and at a higher relative level in HSIL
compared with negative and LSIL Pap tests. Using quantitative methylation data and
ROC analysis, each gene and the 4 genes in combination could distinguish HSIL from
combined negative/LSIL Pap tests. However, the overall sensitivity is relatively low.
These results demonstrate that methylation analysis of gene promoters has
comparable sensitivity and potentially better specificity in comparison to usual
cytomorphological assessment of cytology and Hr‐HPV detection. Although testing for
DNA methylation holds promise as an adjunct to the Pap test, further studies are
needed to identify additional genes that are selectively methylated in HSIL/SCC and to
determine the optimal combination of genes that will provide increased clinical
sensitivity while maintaining high specificity.
References
Fackler MJ, McVeigh M, Mehrotra J, Blum MA, Lange J, Lapides A, Garrett E, Argani
P, Sukumar S. Quantitative multiplex methylation‐specific PCR assay for the
detection of promoter hypermethylation in multiple genes in breast cancer. Cancer
Res. 2004;64:4442‐52.
Fackler MJ, Malone K, Zhang Z, Schilling E, Garrett‐Mayer E, Swift‐Scanlan T, Lange
J, Nayar R, Davidson NE, Khan SA, Sukumar S. Quantitative multiplex
methylation‐specific PCR analysis doubles detection of tumor cells in breast ductal
fluid. Clin Cancer Res. 2006;12:3306‐10.
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Feng Q, Balasubramanian A, Hawes SE, Toure P, Sow PS, Dem A, Dembele B,
Critchlow CW, Xi L, Lu H, McIntosh MW, Young AM, Kiviat NB. Detection of
hypermethylated genes in women with and without cervical neoplasia. J Natl
Cancer Inst. 2005;97:273‐82.
Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB. Methylation‐specific PCR: a
novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A.
1996;93:9821‐6.
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev
Genet. 2002;3:415‐28.
Kahn SL, Ronnett BM, Gravitt PE, Gustafson KS. Quantitative methylation‐specific
PCR for the detection of aberrant DNA methylation in liquid‐based Pap tests.
Cancer. 2008;114:57‐64.
Lai HC, Lin YW, Huang TH, Yan P, Huang RL, Wang HC, Liu J, Chan MW, Chu TY,
Sun CA, Chang CC, Yu MH. Identification of novel DNA methylation markers in
cervical cancer. Int J Cancer. 2008;123:161‐7.
Laird PW. The power and the promise of DNA methylation markers. Nat Rev Cancer.
2003;3:253‐66.
Lee JS, Fackler MJ, Teo WW, Lee JH, Choi C, Park MH, Yoon JH, Zhang Z, Argani P,
Sukumar Quantitative promoter hypermethylation profiles of ductal carcinoma in
situ in north american and korean women: Potential applications for diagnosis.
Cancer Biol Ther. 2008;7:1400‐8.
Schmitt FC, Longatto‐Filho A, Valent A, Vielh P. Molecular techniques in cytopathology
practice. J Clin Pathol. 2008;61:258‐67.
von Knebel‐Doeberitz M, Syrjänen KJ. Molecular markers: how to apply in practice.
Gynecol Oncol. 2006;103:18‐20.
Wisman GB, Nijhuis ER, Hoque MO, Reesink‐Peters N, Koning AJ, Volders HH,
Buikema HJ, Boezen HM, Hollema H, Schuuring E, Sidransky D, van der Zee AG.
Assessment of gene promoter hypermethylation for detection of cervical neoplasia.
Int J Cancer. 2006;119:1908‐14.
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Special lecture (3)
Application of molecular technique on cytologic specimen;
Breast Cancer
Shinobu Umemura, MD.*, Hitoshi Itoh, CT. MIAC**, Akihiko Serizawa, CT.**,
Yoshiyuki R. Osamura, MD, FIAC*
*Department of Pathology, Tokai University School of Medicine
**Division of Diagnostic Pathology, Tokai University Hospital
Cytologic specimens contain abundant information not only morphological but also
genetic and non-genetic findings. We occasionally encounter the patients whose cytologic
materials are only information about breast cancer cells during long time clinical course.
The technical methods to obtain genetic or non-genetic characteristics from these
cytologic materials can provide us much useful informations.
We introduce such kinds of techniques including fluorescence in situ hibyridization
(FISH), chromogenic in situ hybridization (CISH) and direct sequence analysis followed
by laser captured microdissection (LCM). Especially about FISH, we will demonstrate
that cytologic material has a potential to provide more accurate number of centromere
to estimate polysomy by FISH.
The clinical and pathological significance of techniques on cytologic specimens of
breast cancers will be presented.
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Special lecture (4)
Cytological characteristics and differentiation of small
adenocarcinoma of the lung
Reiji Haba
Department of Diagnostic Pathology, University Hospital, Faculty of Medicine, Kagawa University
Thanks to the development of imaging CT, many small lesions have been found in the
lung. Because of the final diagnosis of the patient, various cytological examinations have
been done. Thus, knowledge of the characteristics of the cytology in pulmonary small
lesions is needed. Here we report the cytological characteristics and differentiation of
small adenocarcinoma of the lung.
We examined surgically-resected small peripheral lesions with the greatest dimension
of 2 cm or less. Totally there were 461 cases over the past 9 years at Kagawa
University Hospital: adenocarcinoma, 214 cases (about 50%); other malignant tumors, 54
cases; metastatic tumors, 68 cases; AAH, 24 cases; benign tumors, 12 cases; and
non-tumors, 89 cases. We reclassified only adenocarcinoma using the Noguchi
classification: Type A, 35 cases; Type B, 34 cases; Type C, 106cases; Type D, 9 cases;
Type E, 7 cases; and Type F, 23 cases. We studied especially 10 characteristics of the
stump cytology of the tumor cut surface, and compared these findings with other small
pulmonary lesions.
By low-power Pap stain, cellularity wasminimal in type A and B, and small clusters
were observed with sheet-like and solitary cells. In type C, nuclear overlapping was
often seen. In type D, E, and F, cellularity was abundant, and nuclear overlapping was
seen. By high-power Pap stain, small round nuclei with regular distribution of fine
chromatin were observed in type A and B, together with nuclear irregularity. In type C,
nuclear anisokaryosis, enlargement and irregularity were observed, compared with type
A and B. In type D, E and F, adenocarcinoma is readily diagnosed. In particular, a
tubular formation was observed in type E, and a columnar structure was observed in
type F. Next, we examined the cytology of 48 non-invasive, 68 invasive, and 22
advanced adenocarcinomas. Cellularity was more abundant in an advanced lesion, and
cell cohesion and nuclear overlapping were prominent. We subdivided type C into 31
early invasive carcinomas and 37 invasive carcinomas. The cytology of early invasive
carcinoma was similar to BAC.
Given the cytological characteristics and differentiation of mucinous BAC, mucinous
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adenocarcinoma,
and
mucoepidermoid
carcinoma,
we
must
be
careful
not
to
overdiagnosis non-tumor lesions of the lung. Especially scar, organizing pneumonia,
pulmonary infarction, tuberculosis, and interstitial pneumonia are important. Finally, I
wish to show the cytological characteristics and differentiation of AAH, sclerosing
hemangioma, and papillary adenoma.
In conclusion, using HRCT imaging and clinical information, we must differentiate
small adenocarcinoma from various pulmonary lesions. For example, benign atypical
epithelium, infectious and tumor-like lesion, benign tumor, and other malignant tumors
including metastatic carcinoma. So if we know the cytological characteristics, it is
almost always possible to differentiate adenocarcinoma and other lesions.
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Poster discussion and closing
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Chairpersons : Professor Kiyomi Taniyama
Professor Chang-Hun Lee
Part II (11 - 21) ·
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· 33
Chairpersons : Professor Tatsuo Sawada
Professor Hye-Kyung Lee
****8
Poster
presentation
【Part I】
Chairpersons: Professor Kiyomi Taniyama
Professor Chang Hun Lee
1. High-grade endometrial stromal sarcoma of the uterus: A case report
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Harue Tsugawa, CT , Yosuke Kawakami, MD , Tamaki Toda, CT , Toshinao
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Nishimura, CT , Junichi Sakane, CT , Kazuya Kuraoka, MD , Akihisa Saito,
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2
2
DDS , Satoko Oshita, MD , Kazuhiro Takehara, MD , Masatoshi Kumagai, MD ,
2
2
2
Osamu Samura, MD , Tomoya Mizunoe, MD , Fumitaka Saji, MD , and Kiyomi
3
Taniyama, MD
1
2
3
Departments of Diagnostic Pathology, Obstetrics and Gynecology, and Institute for Clinical
Research, NHO Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
2. Utility of Thyroid Transcription Factor 1 and CDX-2 in Determining the Primary Site of
Metastatic Adenocarcinomas in Serous Effusion
[Jo-Heon Kim], Young Kim, Byung-Woo Min, Yoo-Duk Choi, Jong-Hee Nam, Chan
Choi, Sang-Woo Juhng, Ji-Shin Lee
Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea
3. Peritoneal Fluid Cytology of Malignant Brenner Tumor of the Ovary: A Case Report
1)
1)
1)
Atsuko Okamoto , C.T., Kayo Mitarai , C.T., Masahiro Yoshimori , C.T.,
1)
1)
1)
Nobuhiro Wakabayashi , C.T., Hijiri Sakamoto , C.T., Nobutoshi Tanaka , C.T.,
1)
1)
2)
Akio Sakatani , M.D., Hiromi Egawa , M.D., Takafumi Oshita , M.D., Hirotoshi
2)
2)
3)
Tanimoto , M.D., Nobutaka Nagai , M.D., Kiyomi Taniyama , M.D., Mayumi
1)
Kaneko, M.D.
1)
2)
Department of Pathology, Department of Obstetrics and Gynecology, Hiroshima City Asa
3)
Hospital, Institute for Clinical Research, NHO Kure Medical Center and Chugoku Cancer
Center, Kure, Japan
4. Usefulness of liquid based sputum specimen as a screening method for cytologic
examination and detecting mycobacterium tuberculosis
[Sung-Sun Kim], Yoo-Duk Choi, Chang-Woo Han, Ji-Shin Lee, Jae-Hyuk Lee,
Min-Cheol Lee, Jong-Hee Nam, Chang-Soo Park
Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea
5. Lymphoepithelial carcinoma of the epipharynx: report of two cases
1
1
1
Akihisa Saito, DDS , Toshinao Nishimura, CT , Junichi Sakane, CT , Tamaki
1
1
1
2
Toda, CT , Satoko Oshita, MD , Kazuya Kuraoka, MD , Hiromi Furuya, MD ,
- 31 -
2
2
3
Yoshiyuki Nishi, MD , Haruo Hirakawa, MD , and Kiyomi Taniyama, MD .
1
2
3
Departments of Diagnostic Pathology, Otolaryngology, and Institute for Clinical Research,
NHO Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
6. HPV L1 Capsid Protein in HPV16 Positive Cervicovaginal Smears
1
2
1
1
1
Tae-Jung Kim , SungJong Lee , Ahwon Lee , Eun Sun Jung , Yeong-Jin Choi ,
1
2
Kyo-Young Lee , JongSup Park
1
2
Department of Hospital Pathology, Department of Obstetrics and Gynecology, Kangnam St.
Mary’s Hospital, Catholic University of Korea, Seoul, Korea
7. Utility of pancreatic duct brushing for diagnosis of pancreatic carcinoma and
comparison of cytologic feature in pancreatic or bile juice.
1
1
1
Yoshio Kushida , M.D., Toshitetsu Hayashi , M.D., Kyuichi Kadota , M.D., Naomi
1
1
1
2
Katsuki , M.D., Yumi Miyai , M.D., Kenji Bando , M.D., Eiichiro Hirakawa , M.D.,
3
3
1
Hideki Kamada , M.D., Naohito Uchida , M.D., Reiji Haba , M.D..
1
Department of Diagnostic Pathology, University Hospital, Faculty of Medicine, Kagawa University.
Laboratory of Pathology, Department of Medical Technology, Faculty of Health Sciences,
Kagawa Prefectural College of Health Sciences.
3
Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University.
2
8. The ASCUS cases in cervical cytology; correlation with histological diagnosis and HPV
study
[Sang-Ho Lee], Young-Hye Kim, Hye-Yoon Chang, Hoi-Seon Jeong, Bong-Kyung
Shin, In-Sun Kim, Ae-Ree Kim
Department of pathology, Korea University Guro Hospital
9. A case of Bellini duct carcinoma showing dissemination in ascites
1)
3)
2)
Kiyotaka Wakui ,C.T.,I.A.C., Yuji Nonami ,C.T.,I.A.C., Tatsuo Sawada , M.D.,
2),3)
2),3)
Tomoko Yamamoto ,M.D.,Makio Koboyashi , M.D.
1)
Department of Clinical Laboratory Pathology, Akiru Municipal Medical Center.
Department of Pathology, Tokyo Women’s Medical University.
3)
Department of Surgical Pathology, Tokyo Women’s Medical University.
2)
10. Comparison of Catch by Gene HPV-DNA assay (CBG HPV) and Digene Hybrid
Capture II (HCII) for detection of High-Risk HPV DNA in Cervical Specimens
1
2
Hee-Jae Joo, Tae-Hee Lee, Hyu-Hyee Yim, Sang-Yong Song , Sung-Rim Kim ,
Se-Hwa Sohn
1
Department of Pathology, Ajou University Hospital, Samsung Medical Center,
Medplan Laboratory Center
2
- 32 -
【Part 2】
Chairpersons: Professor Tatsuo Sawada
Professor Hye Kyung Lee
11. A case of oxyphilic papillary carcinoma of the thyroid gland
Junko Tanizawa1), C.T., Mayumi Kozai1), C.T., Kazuko Hasegawa1), C.T., Yachiyo
Yamamoto1), C.T., Tomoko Manabe1), C.T., Tadao Shiooka1), C.T., Shigemi
Kinouchi1), M.T., Masayuki Nakano1), C.T., Yasunobu Funamoto2), C.T., Kyuichi
Kadota2), M.D., Yoshio Kushida2), M.D., Reiji Haba2), M.D.
Shikoku Cytopathological Laboratory1), Department of Diagnostic Pathology, Kagawa University
Hospital, Faculty of Medicine, Kagawa University2)
12. Comparative Analysis of Oligonucleotide Microarray(HPV DNA Chip) and Hybrid
Capture II Assay
Hee-Jae Joo, Tae-Hee Lee, Hyu-Nyee Yim, Sang-Yong Song1, Sung-Rim Kim2,
Se-Hwa Sohn
1
Department of Pathology, Ajou University Hospital, Samsung Medical Center,
Medplan Laboratory Center
2
13. A case of MALT lymphoma of the lung
K. Hasegawa1，R. Ouchi1，J. Tanizawa1，K. Hosoi1，R. Yamanishi1，Y. Furuichi1，
M. Shiraishi1，M. Nakano1，Y. Shirai2，K. Kadota3，Y. Kushida3，R. Haba3
1
Shikoku Cytopathological Laboratory
Department of Clinical Laboratory, Yashima General Hospital　3
Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University
2
14. Comparison of SurePath, conventional smear and cell block preparation in the
evaluation of bronchial washing specimen in lung cancer patients
Hyunee Yim, Young Sook Kwon, Seung Jeong Cho, Hee Jae Joo
Department of Pathology, Ajou University Hospital, Suwon, Korea
15. Intraoperative cytology of orbital chordoid meningioma: a case report , review of the
literature and distinction from other myxoid/mucoid tumors
Hayashi T, Kushida Y, Haba R, Katoda R, Katsuki N, Bando K, Miyai Y,
Tsuzuki Y, Funamoto Y
Department of diagnostic pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
16. Cytologic Features of Malignant Mesothelioma in Body Fluids. -Special Reference on
Differential Diagnosis from Metastatic AdenocarcinomaBaek-Hui Kim1, Ghee-Young Choe1,2, Jin-Hang Chung1,2
1
Department of pathology, Seoul national university Bundang hospital, Seoul, Korea,
- 33 -
2
Department of pathology, college of medicine, Seoul national university, Seoul, Korea.
17. Immunocytochemistry"@to CEA and CD15 of reactive mesothelial cells, Malignant
mesothelioma cells and pulmonary adenocarcinoma cells.
Sadayuki Hiroi, Kuniaki Nakanishi, Sho Ogata, Susumu Tominaga, Masato
Takenaga*, Yoshiki Hiramatsu*, Shizuo Hagiwara* and Toshiaki Kawai
Department of pathology and Laboratory Medicine, National Defense Medical College,
*
Tokorozawa, Saitama, Japan Nichirei Biosciences Inc, Tokyo, Japan
18. The Result of Necrosis on Cytologic Smear in Fine Needle Aspiation of Neck Lymph
Nodes
Jung-Hyun Bae, [Sung‐Wook Hwang], Ji‐Young Park
Department of Pathology, Kyungpook National University Hospital, Daegu, Korea
19. Cytology of Poorly Differentiated Thyroid Carcinoma
1)
2)
Mitsuyoshi Hirokawa , M.D., F.I.A.C., Atsuhiko Sakamoto , M.D., F.I.A.C.,
1)
1)
1)
Miyoko Maekawa , C.T.,I.A.C., Yukari Yanase , C.T.,I.A.C., Seiji Kuma , M.D.,
3)
and Akira Miyauchi , M.D.,
1)
Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe
Department of Pathology, Kyorin University School of Medicine, Tokyo
3)
Department of Surgery, Kuma Hospital, Kobe
2)
20. Differential diagnosis between basal cell adenoma and adenoid cystic carcinoma of
salivary gland in cytologic specimen
Woong Na, Se‐Min Jang, Young‐Jin Jun, Young‐Ha Oh, Moon‐Hyang Park
Department of pathology, Hanyang University College of medicine
21. A Case of Primary Small Cell Carcinoma of the Breast
1)
1)
1)
Yumi Miyai(MD) , Yoshio Kushida(MD) , Toshitetsu Hayashi(MD) , Kyuichi
1)
1)
2)
2)
Kadota(MD) , Naomi Katsuki(MD) , Katsuyuki Noma(CT) , Yoshihito Yano(CT) ,
2)
3)
1)
Masashi Ishikawa(MD) , Eiichiro Hirakawa(MD) , Reiji Haba(MD)
1)
Department of Diagnostic Pathology, University Hospital, Faculty of Medicine, Kagawa University
Department of Pathology, Saiseikai Imabari Hospital
3)
Department of Medical Technology, Faculty of Health Sciences, Kagawa Prefectural College of
Health Sciences
2)
- 34 -
【P-1】
High‐grade endometrial stromal sarcoma of the uterus:
A case report
1
2
1
Harue Tsugawa, CT , Yosuke Kawakami, MD , Tamaki Toda, CT ,
Toshinao Nishimura, CT1, Junichi Sakane, CT1, Kazuya Kuraoka, MD1, Akihisa Saito, DDS1,
1
2
2
Satoko Oshita, MD , Kazuhiro Takehara, MD , Masatoshi Kumagai, MD ,
2
2
2
Osamu Samura, MD , Tomoya Mizunoe, MD , Fumitaka Saji, MD , and
Kiyomi Taniyama, MD3
Departments of 1Diagnostic Pathology, 2Obstetrics and 3Gynecology, and
Institute for Clinical Research, NHO Kure Medical Center and
Chugoku Cancer Center, Kure, Japan.
Background: Endometrial Stromal Sarcomas (ESS) are the least common of the
uterine sarcomas occurring in post‐menopausal women. They consist of 0.5 % of all
uterine corpus sarcomas. Histologically, they are divided into low‐ and high‐grade
tumors, with the latter indicating a poor prognosis. They are often difficult to diagnose
by pre‐operative image analyses or biopsy due to their deep location in the muscle layer
of uterine corpus. In the present case, a pre‐operative cytology method was very useful
for management of the patient.
Case: A 65‐year‐old Japanese woman, gravida 3, para 2 complaining of irregular
genital bleeding consulted a primary care physician. An enlarged uterus and a tumor‐
like lesion were identified on an ultrasound examination, and she was transferred to the
KMC&CCC. Further examination by MRI revealed an enlargement of the uterine lumen
occupied by a tumor originating in the uterine wall. Serum CA‐125 was elevated at 97
IU/ml (<34 IU/Ml), but serum levels of CEA and CA19‐9 were within normal limits. At
the uterine colposcopy, a tumor was evacuated from the uterine cervix. Subsequently,
brushing cytology and biopsy of the tumor were carried out, and aspiration cytology of
the endometrium was conducted. Histological specimens consisted of necrotic tissues
only, and were inadequate to make a diagnosis. However, the tumor was cytologically
diagnosed as a sarcoma from the brushing cytology specimens. Surgical resection of
uterus, greater omentum and pelvic lymph nodes was performed. The final histological
diagnosis was a high‐grade ESS of the uterine corpus (Stage Ib, pT1bN0M0). Following
an adjuvant chemotherapy with doxorubicin (5 cycles), the patient is well, nine months
after the initial therapy.
Brushing cytology: Among scattering intermediate or basal types of squamous cells,
many spindle‐shaped or polygonal tumor cells were observed. Pleomorphic nuclei and
- 35 -
prominent nucleolei with a coarse chromatin pattern gathering in small nests or
distributing individually were visualized. No epithelial cells were found. From these
findings, a cytological diagnosis of sarcoma was made with differential diagnoses of
leiomyosarcomas, stromal sarcomas, and carcinosarcomas.
Histology: The resected uterus weighed 850 g. and the protruding tumor from the
muscle layer of uterine fundus measured 13 x 10 cm in size. The tumor was soft and
yellowish in color on the cut surface. Histologically, spindle‐shaped tumor cells were
found to be loosely arranged in a myxoid stroma showing many mitotic figures, and
some bizarre nuclei. Immunohistochemically, tumor cells showed positive reactions
against vimentin, CD10, desmin, alpha‐smooth muscle actin and myoglobin.
Conclusion: Cytological diagnosis should always be carried out along with the
histological diagnosis when a large mesenchymal tumor is suspected in the uterus. The
cytological approach can identify the cytological features, even when they are embedded
in a necrotic tissue by the histological approach.
- 36 -
【P-2】
Utility of Thyroid Transcription Factor 1 and
CDX-2 in Determining the Primary Site of Metastatic
Adenocarcinomas in Serous Effusion
[Jo-Heon Kim], Young-Kim, Byung-Woo Min, Yoo-Duk Choi, Jong-Hee Nam,
Chan Choi, Sang-Woo Juhng, Ji-Shin Lee
Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea
Introduction: Although identification of the primary tumor in patients with
metastatic adenocarcinomas (ACs) has a profound clinical impact, diagnosing the organ
of origin is frequently difficult. Thyroid transcription factor-1 (TTF-1) and CDX-2 are
transcription factors that have been recently proposed as immunohistochemical markers
of pulmonary and gastrointestinal ACs, respectively. The aim of this study is to
evaluate the usefulness of TTF-1 and CDX-2 in determining the primary site of
metastatic ACs in serous effusion.
Material and methods: A total of 85 cell blocks of effusion fluids from metastatic
ACs, previously stained with a panel of antibodies against MOC-31, D2-40, and
calretinin, were selected. The primary sites were determined by tissue confirmation of
the original tumor and chart review. Immunohistochemical staining using antibodies
against TTF-1 and CDX-2 was performed.
Results: The primary sites were the lungs (n = 40), ovaries (n = 6), pancreas (n = 4),
breasts (n = 3), bile ducts (n = 2), and gastrointestinal tract (30), including stomach (n
= 28) and colon (n = 2). The lung ACs showed TTF-1 positivity in 48% (19/40) of cases.
All non-pulmonary ACs lacked TTF-1 staining. Among the 30 gastrointestinal ACs, 9
(30%) (7 from the stomach and 2 from the colon) showed CDX-2 positivity. All
non-gastrointestinal ACs lacked CDX-2 staining. Specificities and positive predictive
values
for
TTF-1
and
CDX-2
equaled
100%
for
metastatic
pulmonary
and
gastrointestinal ACs, respectively.
Conclusion: The results of the current study demonstrated that TTF-1 and CDX-2
are specific marker to separate metastatic pulmonary and gastrointestinal ACs,
respectively from other metastatic ACs in serous effusion, although its sensitivities are
low.
- 37 -
【P-3】
Peritoneal Fluid Cytology of Malignant Brenner Tumor of the
Ovary: A Case Report
1)
1)
1)
Atsuko Okamoto , C.T., Kayo Mitarai , C.T., Masahiro Yoshimori , C.T., Nobuhiro
Wakabayashi1), C.T., Hijiri Sakamoto1), C.T., Nobutoshi Tanaka1), C.T., Akio Sakatani1),
1)
2)
2)
M.D., Hiromi Egawa , M.D., Takafumi Oshita , M.D., Hirotoshi Tanimoto ,
2)
3)
1)
M.D., Nobutaka Nagai , M.D., Kiyomi Taniyama , M.D., Mayumi Kaneko, M.D.
1)
3)
Department of Pathology, 2) Department of Obstetrics and Gynecology, Hiroshima City Asa Hospital
Institute for Clinical Research, NHO Kure Medical Center and Chugoku Cancer Center, Kure, Japan
【Introduction】
Brenner tumors of the ovary are tumors composed of urothelium‐like epithelium set in
a fibrous stroma. Among them, the tumor whose epithelial component shows invasion as
well as benign or borderline nests in some areas is defined as a malignant Brenner
tumor. This tumor comprises of only 0.1% of all ovarian tumors; thus, that the finding
of this tumor cells in body cavity fluid has not been fully documented. Here, we report
the peritoneal fluid cytologic results in a patient with malignant Brenner tumor.
【Case Report】
A 72‐year‐old female presented with abdominal fullness. The computed tomography
and magnetic resonance images revealed multiple tumors in the abdominal cavity and
abundant ascites. Serum examination showed elevation of CA125 to 6093U/mL. Cytology
of the ascites revealed malignant cells, diagnosed initially as adenocarcinoma. Not
knowing the tumor’s primary site, exploratory surgery was performed along with
bilateral salpingo‐oophorectomy and disseminated tumor resection. The final diagnosis
was malignant Brenner tumor of the right ovary, presenting as a normal‐sized ovary
carcinoma syndrome.
【Cytological Findings in Peritoneal Fluid】
The cytology of the peritoneal fluid revealed relatively small, monotonous atypical
epithelial cells consisting of large papillary clumps with nuclear streaming pattern.
Furthermore, large, irregular shaped pleomorphic atypical cells with coarsely increased
chromatin, distinct nucleoli, and variably light‐green stained cytoplasm were scattered
as a single cell or small cell clusters. Small numbers of the atypical cells had centrally
grooved “coffee‐bean” nuclei or intracytoplasmic mucin.
【Histological Findings】
- 38 -
Urothelium‐like atypical epithelial cells showed invasive growth as a solid‐nest or
papillary pattern. The tumor was composed of medium‐sized monotonous cells
component and large pleomorphic cells components with high‐grade atypia, intermingled
with each other. Furthermore, at the periphery of the tumor, less atypical urothelium‐
like cells grew as solid nests, forming benign Brenner nests.
【Conclusion】
Due to some of the atypical epithelial cells with intracytoplasmic mucin, we
misdiagnosed the malignant Brenner tumor as adenocarcinoma. When epithelial cells
with highly varied degree of nuclear atypia, “coffee‐bean” nuclei, and streaming nuclear
arrangement are present in ascites, malignant Brenner tumor should be considered as
one candidate for differential diagnosis.
* This is a selected paper for the annual award 2008 of Hiroshima‐prefecture branch
of Japanese Society of Clinical Cytology.
- 39 -
【P-4】
Usefulness of liquid based sputum specimen as a screening
method for cytologic examination and detecting
mycobacterium tuberculosis
[Sung-Sun Kim], Yoo-Duk Choi, Chang-Woo Han, Ji-Shin Lee, Jae-Hyuk Lee,
Min-Cheol Lee, Jong-Hee Nam, Chang-Soo Park
Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea
Introduction
Liquid based sputum specimen was recently introduced as a screening method for
examining lung malignancy in many institutes. Another common problem found in
pulmonary department is the mycobacterium tuberculosis (MTB). An essential element
in control of MTB is a rapid and sensitive identification of the causative agent. At
present, the diagnosis of MTB is mostly commonly made by using histologic examination
and culture. Tissue biopsy is an invasive method and has a low sensitivity and
specificity. Culture have to incubated for 2 to 8 weeks before a final diagnosis can be
made. The most promising approach to solve this problem is polymerase chain reaction
(PCR) technique. This study was undertaken to determine the usefulness of liquid based
sputum specimens as a screening method for cytologic examination and detecting the
MTB using MTB-PCR
Material and methods
We collected 718 cases of the liquid based sputum specimens (CellPrep, Medimex co.,
Seongnam) that had been submitted for routine cytologic examination. The samples
were equally divided into two. The one was used for cytologic examination. The other
was used for the absoluteTM MTB-PCR (Biosewoom Inc., Seoul). MTB culture using
another sputum sample submitted at same day was performed in 631 of 718 cases.
Results
Of 718 sputum samples, 69 samples (9.6%) were positive in absoluteTM MTB-PCR. Of
631 sputum culture samples, 51 samples (8.1%) were positive in MTB culture. MTB
DNA was detected in 47 of 51 culture positive samples. Comparing to sputum culture,
the sensitivity, specificity, positive predictive value, and negative predictive value of the
absoluteTM MTB-PCR were 92.2%, 97.2%, 74.6%, and 99.3%. MTB-PCR results were
available within 1 days, compared with an average of 3 weeks for culture of MTB. Of
- 40 -
580 culture negative cases, MTB-PCR was positive in 16 cases (2.8%). Of these patients,
7 patients were suspected of having pulmonary MTB on the basis of pulmonary
infiltrates on their chest X rays. 5 patients had a past history of old pulmonary MTB.
The remaining 4 patients had no clinical history of pulmonary MTB. In cytologic
examination of 781 sputum samples, malignant cells were detected in 28 samples. These
cases were confirmed as malignancy at lung biopsy that was subsequently performed.
Conclusion
Thess data establish the utility of the MTB PCR test for rapid detection of MTB in
liquid based sputum sample. Because it was concomitantly used in cytologic examination, it could be proposed as screening method for detecting malignany and MTB.
- 41 -
【P-5】
Lymphoepithelial carcinoma of the epipharynx:
report of two cases
1
1
1
1
Akihisa Saito, DDS , Toshinao Nishimura, CT , Junichi Sakane, CT , Tamaki Toda, CT ,
Satoko Oshita, MD1, Kazuya Kuraoka, MD1, Hiromi Furuya, MD2, Yoshiyuki Nishi, MD2,
2
3
Haruo Hirakawa, MD , and Kiyomi Taniyama, MD .
1
2
3
Departments of Diagnostic Pathology, Otolaryngology, and Institute for Clinical Research,
NHO Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
Background:
Although
relatively
common
in
south
China,
lymphoepithelial
carcinoma of the epipharynx is very rare in Japan. Recently, we experienced two such
cases.
Cases: Separately, a 50s‐year‐old Japanese woman and an 80s‐year‐old Japanese man
complaining of a headache consulted our hospital. MRI examination revealed a
1.8x0.7cm epipharyngeal tumor in the female patient while the male patient had an
invasive tumor into the scalp base of the epipharynx. Both patients underwent needle
biopsy with stamp cytology performed on the biopsy specimens. After the receiving the
histopathological and cytological diagnosis of lymphoepithelial carcinoma, the tumor of
each patient was irradiated with good effects.
Cytology: Atypical epithelial cells clusters were scattered among many small
lymphocytes. These epithelial cells were large and had centrally located nuclei showing
an increased N/C ratio and prominent nucleoli. In the male case, three dimensional cells
clusters were also observed. Cells in the cluster differed in size and had spherical or
spindle‐shaped nuclei. The nucleus had an irregular shape with increased chromatin. In
the female patient, the cytological diagnosis was suspicious of a lymphoepithelial
carcionoma while in the male patient lymphoepithelial carcinoma was confirmed.
Histopathology:
Biopsy
specimens
revealed
the
features
of
lymphoepithelial
carcinoma.
Conclusion: Lymphoepithelial carcinoma is highly sensitive to irradiation. Prompt
cytological diagnosis will benefit the tumor treatment.
- 42 -
【P-6】
HPV L1 Capsid Protein in HPV16 Positive Cervicovaginal Smears
Tae-Jung Kim1, Sung-Jong Lee2, Ah-Won Lee1, Eun-Sun Jung1, Yeong-Jin Choi1,
1
2
Kyo-Young Lee , Jong-Sup Park
1
2
Department of Hospital Pathology, Department of Obstetrics and
Gynecology, Kangnam St. Mary’s Hospital, Catholic University of Korea, Seoul, Korea
Background: It is well known that the most of cervical lesions are associated HPV
infection. The integration of HPV DNA into host cell DNA is considered to promote
selective carcinogenesis. After integration of HPV DNA, the production of HPV L1
capsid protein, the target of host immunity, disappears, which provides the information
of whether HPV DNA is integrated or not.
Material and method: From January 2007 to December 2007, 127 HPV16 positive
cervicovaginal smears were immunostained by L1 capsid antibody, using HPV L1 capsid
protion detection kit. The results were compared with the the results of PAP cytology.
Result: 26% (33/127) of total cases, 10% (5/50) of normal cytology, 31.6% (6/19) of
ASUCUS,
56%
(14/25)
of
LSIL
,and
36.4%
(8/22)
of
HSIL
reveal
positive
immunoreactivity for L1 capsid protein, None of 11 squamous cell carcinoma (SCC)
cases reveal L1 capsid protein immunoreactivity.
Conclusion: The positive rate of L1 capsid protein was lower in HSIL lesions than
LSIL lesion. All of SCC cases were negative for L1 capsid protein. This is indirect
evidence that HPV DNA integration to hostcell DNA is more frequent in HSIL or SCC
than LSIL. The loss of L1 capsid protein could be regarded as a surrogate marker of
HPV DNA integration, which is considered as a poor prognostic factor in cervical
premalignant lesion, and used as a adjunctive tool for treatment and follow up
planning.
- 43 -
【P-7】
Utility of pancreatic duct brushing for diagnosis of
pancreatic carcinoma and comparison of cytologic feature in
pancreatic or bile juice.
1
1
1
1
Yoshio Kushida , M.D., Toshitetsu Hayashi , M.D., Kyuichi Kadota , M.D., Naomi Katsuki ,
M.D., Yumi Miyai1, M.D., Kenji Bando1, M.D., Eiichiro Hirakawa2, M.D., Hideki Kamada3,
3
1
M.D., Naohito Uchida , M.D., Reiji Haba , M.D..
1
2
Department of Diagnostic Pathology, University Hospital, Faculty of Medicine, Kagawa University.
Laboratory of Pathology, Department of Medical Technology, Faculty of Health Sciences, Kagawa
Prefectural College of Health Sciences.
3
Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University.
INTRODUCTION: Although cytologic examination of pancreatic or bile juice has
been useful for the diagnosis of pancreatic carcinoma, we often experience not to be able
to make an appropriate diagnosis because there are no or a few carcinoma cells with
conspicuous degeneration. On the other hand, pancreatic duct brushing is increasingly
being used for the diagnosis of pancreatic carcinoma. We evaluate the usefulness of
pancreatic duct brushing, and compare cytological findings with direct smears of
pancreatic or bile juice.
MATERIAL AND METHOD: We reviewed the case files of pancreatic carcinomas
examined from January 1997 to July 2008 in Kagawa University Hospital. Pancreatic or
bile juices were obtained from 40 patients and pancreatic duct brushing was performed
on 48 patients.
RESULTS: The cytologic findings of pancreatic or bile juice were as follows: benign
25% (n=10), malignant 35% (n=14), suspicious for malignancy 35% (n=14), and
inadequate 5% (n=2). The brushing cytology results were: benign 12% (n=6), malignant
73% (n=35), and suspicious for malignancy 15% (n=7). Number and size of cell clusters
tended to be larger in brushing specimen than pancreatic or bile juice. Malignant cells
of pancreatic or bile juice showed more pyknotic, greater angularity and irregular
nuclei, unclear nucleoli, and thick cytoplasm than brushing specimens.
CONCLUSION: In brushing specimens, a better appreciation of cytologic features
when compared with direct smears. Therefore, pancreatic duct brushing is useful for
diagnosis of pancreatic carcinoma. It is important to understand the cytologic
characteristics in each specimen and to be used to flesh cells.
- 44 -
【P-8】
The ASCUS cases in cervical cytology; correlation with
histological diagnosis and HPV study
[Sang-Ho Lee], Young-Hye Kim, Hye-Yoon Chang, Hoi-Seon Jeong, Bong-Kyung Shin,
In-Sun Kim, Ae-Ree Kim
Department of pathology, Korea University Guro Hospital
Background : Cervical cytology is a very effective, inexpensive, and non‐invasive test.
ASCUS (Atypical squamous cells of undetermined significance) is the cytologic change
suggestive of squamous intraepithelial lesion, but not sufficient for a definitive
interpretation. We evaluated the corresponding histological findings of ASCUS and
examined if the presence of HPV infection and the viral titer could be correlated with the
histologic features.
Methods : We evaluated 600 ASCUS cases from January 2006 to September 2008 in
Korea university Guro hospital. The histological diagnoses were confirmed by cervical
punch biopsy, conization, or hysterectomy. High risk HPV groups (16, 18, 31, 33, 35, 39,
®
45, 51, 52, 56, 58, 59, and 68) were detected by hybrid capture method and the DNA
titer was measured.
Result : Among the six hundred ASCUS cases, chronic cervicitis were 341 cases
(56.8%), borderline condylomas were 93 cases (15.5%), condyloma accuminata 6 cases
(1%), flat condylomas 63 (10.5%), mild dysplasias 36 (6%), moderate dysplasias 18 (3%),
severe dysplasias 23 (3.8%), squamous cell carcinomas 17 (2.8%), and adenocarcinomas
were 3 (0.5%) cases. The positive HPV results were observed in 157 cases of chronic
cervicitis (46%, mean HPV titer : 80.39), 70 cases of borderline condyloma (75.3%, mean
HPV titer : 190.92), 2 cases of condyloma accuminatum (33.3%, mean HPV titer : 263.6),
63 cases of flat condyloma (77.8%, mean HPV titer : 303.91), 36 cases of mild dysplasia
(58.3%, mean HPV titer : 135.14), 18 cases of moderate dysplasia (88.9%, mean HPV
titer : 654.92), 23 cases of severe dysplasia (95.7%, mean HPV titer: 285,90), 10 cases of
squamous cell carcinoma (58.8%, mean HPV titer : 253.90). Among the diagnostic groups,
the chronic cervicitis showed significantly lower rate of high‐risk HPV infection than all
the other diagnostic entities (p<0.001). The difference in mean HPV titer was most
prominent between of the chronic cervicitis and moderate dysplasia groups (p=0.046).
Conclusions : ASCUS in cervical cytology may be various different histological
entities from benign inflammation, dysplasia to definite malignancy. The high‐risk HPV
infection rate and viral titer in ASCUS can show statistically significant differece among
the histological groups. Thus, among the patients with ASCUS in cervical cytology, the
HPV study may be useful as an ancillary test.
- 45 -
【P-9】
A case of Bellini duct carcinoma showing dissemination in ascites
Kiyotaka Wakui1) ,C.T.,I.A.C., Yuji Nonami3),C.T.,I.A.C., Tatsuo Sawada2), M.D.,
2),3)
Tomoko Yamamoto
2),3)
,M.D.,Makio Koboyashi
, M.D.
1)
Department of Clinical Laboratory Pathology, Akiru Municipal Medical Center.
2)
Department of Pathology, Tokyo Women’s Medical University.
3)
Department of Surgical Pathology, Tokyo Women’s Medical University.
Carcinoma of the collecting ducts of Bellini (Bellini duct carcinoma) is rare, accounting
for less than 1% of renal malignancies. We present a case of Bellini duct carcinoma
showing carcinoma cells in ascites in a man of 30's, who complained left back pain. CAT
scan examination revealed dilatation of abdominal space and enlargement of the left
kidney and adrenal gland. Tumor formation was also seen in the subcutaneous tissue of
the left back. Aspiration cytology from ascites showed numerous atypical cells with
showing low N/C ratio. Atypical cells showed abundant cytoplasm with PAS positive
materials and hyperchromatic nuclei with distinct nucleoli which were dislocated to the
periphery. A few atypical cells showing small cell clusters and multinucleated atypical
cells were accompanied. Cytological diagnosis was poorly differentiated adenocarcinoma,
but the primary site was not specified. In upper and lower digestive systems, no specific
finding were obtained by endoscopic examinations. Needle biopsy and needle aspiration
cytology from the left back tumor revealed bubbles‐shaped epithelial cell cluster which
was similar to atypical cells obtained by previous cytological specimen. Despite of the
enlargement of the left kidney and adrenal gland, we could not conclude the primary
site, because renal and adrenal carcinomas rarely appear in ascites. The patient showed
downhill course, and passed away four months later by hospitalization. On autopsy,
cloudy and dark beer colored asicites of 6,800ml and the enlarged left kidney measuring
16x9x8cm with diffuse infiltration of tumor and forming conglomerated tumor with
retroperitoneum were recognized. Microscopically, tumor cells showed tubular to
papillary growth patterns predominantly, and the hobnail structure was contained in
small areas. Immunohistochemical staining revealed positive staining for cytokeratin
(AE1/AE3) and vimentin in most of the tumor cells. Some cells were positive for
EMA,CK7 and CD15, but negative for CK20 and CD10. The cytological findings of
gastric signet ring cells and this carcinoma cell were very similar. Only foamy and
vacuolated cytoplasm appears to be a characteristic feature of Bellini duct carcinoma
cells, although the differential diagnosis of signet ring cells and Bellini duct cancer cells
are very difficult. Encountering the cancer cells having findings to signet ring cells in
ascites, we should not exclude reteroperitoneal organ origin.
- 46 -
【P-10】
Comparison of Catch by Gene HPV‐DNA assay (CBG HPV) and
Digene Hybrid Capture II (HCII) for detection of High‐Risk
HPV DNA in Cervical Specimens
1
2
Hee-Jae Joo, Tae-Hee Lee, Hyun-Yee Yim, Sang-Yong Song , Sung-Rim Kim ,
Se-Hwa Sohn
1
Department of Pathology, Ajou University Hospital, Samsung Medical Center,
2
Medplan Laboratory Center
BACKGROUND: Human papilloma virus (HPV) is the main cause of cervical cancer
and cervical intraepithelial neoplasia worldwide. At the present day, the incidence of
HPV infection is rising. Detection of high‐risk human papillomavirus has proved its
usefulness in complement of abnormal cervical cytology result. In this study, we have
compared the clinical performance with the CBG HPV DNA Assay kit (Catch By Gene
Co., Wonju, Korea) and Hybrid Capture II (Digene Co., Gaithersburg, MD, USA) on 237
of cervical cytology samples.
MATERIALS and METHODS: 237 samples were suitable for analysis. The samples
were classified to six groups according to Cytological result. 84 (36.4%) of all samples
were WNL, RCC, IE, Clue cell, others 59 (24.9%) samples were ASCUS, 73 (30.8%)
samples were L‐SIL, 16 (6.8%) samples were H‐SIL, 2(0.8%) sample was SCC, 3(1.3%)
samples were Adenocarcinoma. Cervical cytology samples were tested in parallel with
CBG and HCII kit assay. CBG HPV DNA Assay kit was performed the test using
Table. Comparison with the features between CBG HPV and Hybrid Capture II
Catch by Gene (CBG HPV)
Hybrid Capture II (HCII)
Product Name
CBG HPV‐DNA Qualitative assay
HCII HPV DNA Test
Principle
Amplification & Hybridization
Using Colorimetry
DNA‐RNA Hybridization
Using luminometry
Run Time
6 hours
5 hours
Automatic analysis
Can use automatic ELISA system
Incubate at 37℃
Cannot use automatic system
Incubate at 65℃
Result analysis
Compatibility with any other
colorimeter
Use only Digene's system
Sample process capacity
92 tests
90 tests
Possible detecting type
15 types(16,18,31,33,35,39,45,51
52,53,56,58,59,66,68)
13 types(same as CBG
excepted 53,66)　- 47 -
colorimetry by DNA extract, amplify and hybridize. HCII Assay was performed the test
using Chemiluminometry by DNA extract and hybridize by DNA chip assay performed
in 100 cases (included 39 of the discordant cases, which compared the test results of
CBG HPV DNA Assay kit with HCII kit and 61 random selected cases from L‐SIL and
H‐SIL).
RESULTS: The positive results were detected in 231 of 237 cases (97.4%) by CBG
HPV DNA Assay kit and 200 of 237 (84.4%) by HCII assay kit. 196 of 237 samples
(82.7%) were showed concordant result between CBG HPV DNA Assay kit assay and
HCII kit. 66 of 100 samples were showed concordant result for the presence or absence
of HR‐HPV between HCII tests and DNA chip. 80 of these 100 specimens showed
concordant result for the presence or absence of HR‐HPV between CBG HPV‐DNA tests
and DNA chip.
DISCUSSION: The result of CBG HPV was showed higher positive rate than HC II
in ASCUS, L‐SIL and H‐SIL. Degree of concordance between CBG HPV and DNA chip
was higher than between HC II and DNA chip.CBG HPV assay can be used to screen
for the more common High risk HPV.
Figure. Comparison of positive result between CBG HPV, Hybrid Capture II
and DNA chip assay according to Risk group
- 48 -
【P-11】
A case of oxyphilic papillary carcinoma of the thyroid gland
1)
1)
1)
Junko Tanizawa , C.T., Mayumi Kozai , C.T., Kazuko Hasegawa , C.T.,
Yachiyo Yamamoto1), C.T., Tomoko Manabe1), C.T., Tadao Shiooka1), C.T., Shigemi
1)
1)
2)
2)
Kinouchi , M.T., Masayuki Nakano , C.T., Yasunobu Funamoto , C.T., Kyuichi Kadota ,
2)
2)
M.D., Yoshio Kushida , M.D., Reiji Haba , M.D.
Shikoku Cytopathological Laboratory1), Department of Diagnostic Pathology,
2)
Kagawa University Hospital, Faculty of Medicine, Kagawa University
Background: Oxyphilic papillary carcinoma of the thyroid is very rare. We report a
patient with oxyphilic papillary of the thyroid gland, mainly focusing on the findings on
aspiration cytology.
Case: A 1.5‐cm mass was noted by ultrasound examination in the left lobe of the
thyroid gland of a 70‐year‐old woman. Because FDG‐PET showed an increased
uptake(SUV:14), malignancy was suspected. So fine‐needle aspiration cytology was
performed. Many irregular scattered cell clusters were observed. The smear showed
papillary and sheet clusters. The tumor cells contained abundant granular cytoplasm
and had large and round nuclei showing anisokaryosis with prominent nucleoli. Some
nuclear grooves were observed, but no intranuclear cytoplasmic inclusions were seen.
Macroscopically, the tumor measured about 2 cm in size, and its cut surface was
grayish‐white in color. Histologically, forming papillary and follicular architecture, the
tumor cells had rich eosinophilic granular cytoplasm with nuclear anisokaryosis. Cells
showed ground glass nuclei and a partially nuclear groove. Immunohistochemically the
tumor cells were positive for vimentin, CK18, and partially positive for CK19, CK34β
E12, EMA, CD15, CD44, CD57 and HBME‐1. Based on these findings, a diagnosis of
oxyphilic papillary carcinoma was made.
Conclusion: The cytodiagnosis of oxyphilic papillary carcinoma is possible if careful
attention is paid to the nuclear groove, ground glass nuclei and the characteristic
granular cytoplasm.
- 49 -
【P-12】
Comparative Analysis of Oligonucleotide Microarray
(HPV DNA Chip) and Hybrid Capture II Assay
1
2
Hee-Jae Joo, Tae-Hee Lee, Hyun-Yee Yim, Sang-Yong Song , Sung-Rim Kim ,
Se-Hwa Sohn
1
Department of Pathology, Ajou University Hospital, Samsung Medical Center,
2
Medplan Laboratory Center
Background and Purpose. Genetic test of human papillomavrus (HPV) is accepted
as a promising supplementary tool of Pap smear in screening of uterine cervix cancer.
Standard genetic test for HPV is polymerase chain reaction (PCR) followed by
sequencing assay, but is too complex to be done in clinical practice. Much simpler test,
hybrid capture assay (Digene Inc.), is most widely used to detect HPV and screen high
risk HPV. Recently DNA microarray is also beginning to be used not only to detect but
also genotype HPV, but relative advantage of DNA chip over hybrid capture assay
remains ill defined. We herein have comparatively analyzed HPV genotyping DNA chip
(HPV DNA chip, Goodgene Inc.) and hybrid capture assay‐II (HCA‐II).
Materials and Methods. Two hundred one samples of cervical swab samples which
showed abnormality and were suspected of having HPV infection on cytological analysis
was analyzed by PCR followed by automated sequencing assay and genotype specific
PCR assay. These were then comparatively analyzed by HPV DNA chip and HCA‐II.
Results. On the analysis by PCR and sequencing, 191 out of 201 cervical swab
samples showed presence of HPV, 149 infection by high risk type HPV and 72 (37.7%)
mixed infection by more than 1 genotype of HPV, respectively. On HPV DNA chip
analysis, all of 191 samples were accurately identified as having HPV and 174 (91.1%)
including all of the cases with high risk HPV were accurately genotyped. In contrast,
HCA‐II failed to detect HPV in 40 out of 191 cases (20.9%) and missed 12 of 149 (8.1%)
cases with high risk type HPV. HPV DNA chip could detect all of the risky lesions of
cervix including carcinoma, cervical intraepithelial neoplasm and high grade squamous
intraepithelial lesion (SIL), whereas, HCA‐II failed to detect 1 of 8 carcinoma and 1 of
12 high grade SIL. HPV DNA chip was superior to HCA‐II in detection of low grade SIL
(98.3% vs. 55.9%, p<0.05).
Conclusions and Discussion. HPV DNA chip in the present study may be an
excellent tool for the HPV testing. It may be superior to HCA‐II in not only detection
and genotyping of HPV but also screening of cancer and precancerous lesion of the
uterine cervix. Further prospective multicenter study is necessary on HPV DNA chip in
- 50 -
order to confirm these preliminary results.
Key Words : Uterine cervix cancer, human papillomavirus (HPV), DNA chip, hybrid
capture assay, polymerase chain reaction (PCR), sequencing assay.
- 51 -
【P-13】
A case of MALT lymphoma of the lung
1
1
1
1
1
1
K. Hasegawa ，R. Ouchi ，J. Tanizawa ，K. Hosoi ，R. Yamanishi ，Y. Furuichi ，
M. Shiraishi1，M. Nakano1，Y. Shirai2，K. Kadota3，Y. Kushida3，R. Haba3
1
Shikoku Cytopathological Laboratory
Department of Clinical Laboratory, Yashima General Hospital　3
Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University
2
Background: Cases previously described as pulmonary pseudolymphoma are mostly
recognized as MALT lymphoma by molecular techniques recently. We mainly report the
cytological characteristics of primary pulmonary marginal zone B‐cell lymphoma of the
MALT type.
Case: An abnormal shadow was detected by chest X‐ray in a man in his thirties.
Clinically,　organizing pneumonia had been diagnosed. He had been followed for 2 years,
and was admitted for further examination. Chest CT showed an irregular tumor lesion
measuring 51×51 mm in the left lower lobe. Brushing cytology and transbronchial lung
biopsy were performed. Brushing cytology showed many clusters with a predominant
population of small‐to‐intermediate round‐shaped cells with minimal atypia. Sometimes
lymphocytes were intertwined around the ciliated columnar cells. The histological biopsy
specimen revealed dense lymphoid cell
infiltration.
Immunohistochemically,
the
lymphoid cells were positive for CD20, CD43, and CD79α, and negative for CD3, CD5,
and CD10. A monoclonal immunoglobulin heavy chain gene rearrangement was observed
by PCR. MALT lymphoma was highly suspected, and left lower lobectomy was
performed. Histological findings showed small lymphoid cells mainly composed of
centrocyte‐like cells with many lymphoepithelial lesions. Immunohistochemically, CD20,
CD43 and CD79α were positive. And negative for CD3, CD5, and CD10. Imprint
cytology showed intermediate‐sized, and round lymphocytes with smooth nuclear
membranes and scant cytoplasm. Giemsa stain showed centrocyte‐like cells.
Conclusion: It was difficult to diagnose MALT lymphoma on the basis of only
Papanicolaou stain, because it showed minimal atypia of neoplastic lymphoid cells.
However, the cytological findings, for example, the abundance of lymphoid tissue and
high proportion of intermediate centrocyte‐like cells, were important. In addition,
immunocytochemical stainings and molecular techniques were useful in making the
cytological diagnosis in this case.
- 52 -
【P-14】
Comparison of SurePath, conventional smear and
cell block preparation in the evaluation of bronchial
washing specimen in lung cancer patients
Hyun-Ee Yim, Young-Sook Kwon, Seung-Jeong Cho, Hee-Jae Joo
Department of Pathology, Ajou University Hospital, Suwon, Korea
To evaluate the usefulness in diagnosis of lung cancer, we compare the SurePath,
conventional smear (CS), and cell block preparation (CB) of bronchia washing specimen.
We retrospectively reviewed 3 preparations from 209 patients whose diagnosis was
confirmed later by bronchoscopic biopsy, fine needle aspiration (FNA), gun biopsy or
operation. Slides were reviewed independently without knowing the final histologic
diagnosis. Each slides were categorized as three groups; “Negative for malignancy”,
“Atypical cells or suspicious for malignancy”, and “Malignancy”. Malignant tumors were
later classified into squamous cell carcinoma, adenocarcinoma, small cell carcinoma, or
non small cell carcinoma.
When including the “Atypical cells” and “Malignancy” categories as positive, the
overall sensitivity of each preparations was 74.4% on SurePath, 72.9% on CS, and 76.5
% on CB preparations. Specificity was 98. 7%, 94.7% and 98.7 % , respectively.
In suquamous cell carcinoma, the overall sensitivity was 75.4% on SurePath, 78.9% on
CS, and 77.2% on CB.
Sensitivity of CS and CB in adenocarcinoma was 71.4% ,
compared to 77.2% on SurePath. In small cell carcinoma, sensitivity of SurePath and
CS was 70.4% and sensitivity of CB is 66.7%.
In each type of malignant tumor, “Atypical cells” or “Malignancy” was seen in all
three preparation s in 68.4%, 66.7%, 57.1% of squamous cell carcinoma, adenocarcinoma,
and small cell carcinoma, respectively. Among 133 malignant tumors, 15 cases showed
“Atypical cells” or “Malignancy” in only one preparation; 7 cases (5.2%) on SurePath, 4
cases (3.0%) on CS, and 4 cases (3.0%) on CB.
Despite many advantages of SurePath over CS, overall sensitivity and sensitivity of
SurePath compared to CS and cell block is not significantly high.
Application of all
three methods may be helpful in which the other method is not diagnostically
conclusive.
- 53 -
【P-15】
Intraoperative cytology of orbital chordoid meningioma:
a case report, review of the literature and distinction
from other myxoid/mucoid tumors
Hayashi T, Kushida Y, Haba R, Katoda R, Katsuki N, Bando K, Miyai Y,
Tsuzuki Y, Funamoto Y
Department of diagnostic pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
BACKGROUND: Chordoid meningioma (CM) is an extremely rare subtype of
meningioma in which oval to polygonal cells arranged in a cord‐like pattern on a myxoid
background is observed. The cytology of this peculiar tumor has rarely been reported.
CASE: A 53‐year‐old male presented with a 6‐month history of progressive
exophtalmus of the left eye. CT scan revealed thickened left sphenoid bone compressing
the ipsilateral optic nerve. The patient underwent operation and a poorly circumscribed
mass of 2 x 1.5 x 1 cm with bone involvement was identified. The mass was
incompletely
excised
and
was
composed
of
grey‐bright
gelatinous
tissue.
The
intraoperative squash smears revealed small clusters or cord‐like structures of bland
tumor cells possessing uniformly round nuclei with smooth nuclear membrane, even fine
granular chromatin and small nucleoli. The tumor cells were embedded in an abundant
myxoid background. Coarse cytoplasmic filaments, occasional intranuclear inclusions and
whorl‐like structures were also observed. Due to the abundance of myxoid background,
the differential diagnoses include groups of myxoid/mucoid neoplasms such as myxoid
meningioma, myxoid chondrosarcoma, chordoma, parachordoma, and chordoid glioma.
The diagnosis of CM was confirmed on histopathology and ancillary immunohistochemical studies.
CONCLUSION:
CM has
diagnostic
cytologic
features
which
show
complete
concordance with histology. Distinguishing CM from other myxoid/mucoid neoplasms can
be challenging however if diligent morphologic study and/or ancillary studies are
performed accurate diagnosis is possible.
- 54 -
【P-16】
Cytologic Features of Malignant Mesothelioma in Body Fluids.
-Special Reference on Differential Diagnosis from Metastatic Adenocarcinoma1
1,2
1,2
Baek-Hui Kim , Ghee-Young Choe , Jin-Hang Chung
1
Department of pathology, Seoul national university Bundang hospital, Seoul, Korea,
Department of pathology, college of medicine, Seoul national university, Seoul, Korea.
2
Background : Malignant mesothelioma (MM) is the most frequent primary malignant
neoplasm of serosal membranes and has a poor prognosis. In the aspect of early
detection of MM, body cavity fluid may be one of the most appropriate specimens
avoiding unnecessary invasive diagnostic procedure. However, differentiating MM from
metastatic adenocarcinoma (MA) is the most challenging in the diagnosis of serosal
lesions. The objective of this study is to define characteristic cytologic features of MM
distinct from those of MA.
Materials and Methods : Cytologic specimens of 9 MM, 10 MA and 1 reactive
mesothelial hyperplasia were retrieved from the archival materials in the Department of
Pathology, Seoul National University Bundang Hospital from May 2003 to July 2008.
Several features, such as cellular composition, intracytoplasmic vacuole formation,
intercellular
window
formation,
fuzzy
margin
with
microvilli,
long‐chain
like
arrangement, atypia of underlying scattered single mesothelial cells and infiltration of
inflammatory cells were evaluated. Histologic and immunohistochemical features of
biopsy specimens were compared to cytologic features of body cavity fluid samples.
Results : As distinct from adenocarcinoma, MM consisted of clusters and scattered
singly dispersed malignant cells. The clusters of MM seemed somewhat two‐dimensional
configuration rather than three‐dimensional cell balls in MA. The cellular cluster of MM
showed scalloped borders, intercellular windows and long‐chain like arrangement.
Individual tumor cells of MM showed round to polygonal vacuolated cytoplasm, and lacy
cytoplasmic borders. Infiltration of inflammatory cells such as neutrophils and
lymphocytes were more common in MM than MA. In the case of MA, distinct two
populations of malignant tumor cell clusters and underlying scattered reactive
mesothelial cells were prominent.
Conclusion : In most cases, differential diagnosis of MM from MA in body cavity
fluid was possible based on above cytologic parameters and it was even more helpful
than histopathologic diagnosis of
biopsy samples. Meticulous examination using the
panel of above cytologic parameters would lead to early and accurate diagnosis of
malignant mesothelioma, avoiding misdiagnosis and inappropriate invasive procedures.
- 55 -
【P-17】
Immunocytochemistry　to CEA and CD15 of reactive
mesothelial cells, Malignant mesothelioma cells and
pulmonary adenocarcinoma cells.
Sadayuki Hiroi, Kuniaki Nakanishi, Sho Ogata, Susumu Tominaga, Masato Takenaga*,
Yoshiki Hiramatsu*, Shizuo Hagiwara* and Toshiaki Kawai
Department of pathology and Laboratory Medicine, National Defense Medical College,
Tokorozawa, Saitama, Japan
* Nichirei Biosciences Inc, Tokyo, Japan
Background: Morphologic distinction between Reactive mesothelial cells, Malignant
mesothelioma cells and pulmonary adenocarcinoma cells is frequency difficult.
Carcinoembryonic antigen (CEA) was defined as a tumor‐associated antigen that was
first demonstrated in colon cancer. Subsequently, this antigen was detected also in
pulmonary adenocarcinoma. Cluster of differentiation 15 (CD15) was a marker to
neutrophil. However, well known the positivity is shown adenocarcinoma cells. We
examined the expression of CEA and CD15 by immunocytochemical staining in reactive
mesothelial cells, malignant mesothelioma cells and pulmonary adenocarcinoma cells
and investigated whether or not this method is useful for differentiating reactive
mesothelial cells, malignant mesothilioma cells and pulmonary adenocarcinomacells.
Materials and Methods: Cytology specimens from 13 cases with pleural effusion
including reactive mesothelial cells Imprint cytology specimens from 3 cases malignant
mesothelioma and 32 cases pulmonary adenocarcinoma were immunostained with
antibodies against CEA (MILAB; MCS) and CD15 (Nichirei Biosciences, MCS‐1). The
expression was determined positive or negative by distribution.
Results: Pulmonary adenocarcinoma were immunopositive for CEA only: 24/32 (75%),
and CD15 only: 23/32 (72%) detected in the cytoplasm and cell membrane of
adencarcinoma cells. Positive reaction either of CEA or CD 15 were 28 examples (88%).
However, both reactive mesothelial cells and malignant mesoththelioma cells were
negative.
Conclusions: Detection of CEA and CD15 by immunocytochemical staining may be a
useful adjunct in differentiating adenocarcinoma from malignant mesothelioma cells and
reactive mesothelial cells. The positivity is enhanced when both CEA and CD 15 are
utilized.
- 56 -
【P-18】
The Result of Necrosis on Cytologic Smear in Fine Needle
Aspiation of Neck Lymph Nodes
Jung-Hyun Bae, [Sung-Wook Hwang], Ji-Young Park
Department of Pathology, Kyungpook National University Hospital, Daegu, Korea
Fine needle aspiration (FNA) is a very handy modality by which to evaluate palpable
cervical lymphadenopathy. In Kyungpook National University Hospital, from 1999 to
2007, the authors have performed a review on 89 cases which were diagnosed as
necrosis or necrotic debris by cervical lymph node aspiration and checked by the result
of a Tuberculosis Polymerase chain reaction (Tbc‐PCR) test. Among them, 45 cases
(50%) were confirmed by biopsy as the following; 25 cases as tuberculosis (55.6%), 12
cases as inflammation or necrosis (26.7%), 4 cases as metastatic carcinoma of lymph
node (8.9%), 3 cases as malignant lymphoma (6.7%), and 1 case as necrotizing
lymphadenitis (2.2%). Among 89 cases, 6 cases out of 9 showed positive reaction to Tbc‐
PCR; Only 2 cases out of 6, that showed a positive reaction to Tbc‐PCR, were confirmed
to be tuberculosis upon histopathologic examination. Two cases were diagnosed as
necrosis upon histologic examination. In 2 other cases, tests and further evaluations
were not performed. Those 3 cases that showed a negative reaction to Tbc‐PCR were
diagnosed as tuberculosis by histopathologic examination.
As these 45 cases were confirmed a diagnosis by biopsy, the authors have been able
to compare the pattern of findings of necrosis on cytologic slides with histologic
diagnosis.
Keywords : Fine needle aspiration, lymph node, necrosis
- 57 -
【P-19】
Cytology of Poorly Differentiated Thyroid Carcinoma
1)
2)
Mitsuyoshi Hirokawa , M.D., F.I.A.C., Atsuhiko Sakamoto , M.D., F.I.A.C., Miyoko
1)
1)
1)
Maekawa , C.T.,I.A.C., Yukari Yanase , C.T.,I.A.C., Seiji Kuma , M.D., and Akira
Miyauchi3), M.D.,
1)
Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe
Department of Pathology, Kyorin University School of Medicine, Tokyo
3)
Department of Surgery, Kuma Hospital, Kobe
2)
Background: In 1983, Sakamoto et al. proposed poorly differentiated carcinoma
(PDC) of the thyroid as a clinicopathologic entity for a high-risk group of papillary and
follicular thyroid carcinomas. In 2004,World Health Organization (WHO) defined PDCas
follicular-cell neoplasms that show limited evidence of structural follicular cell
differentiation and occupy both morphologically and behaviorally an intermediated
position between differentiated (follicular and papillary carcinomas) and undifferentiated
(anaplastic) carcinomas. However, different diagnostic criteria have beenemployed,
resulting in wide discrepancies and confusion. Therefore, cytologic findings of PDC have
not been clear. A purpose of this study is to clarify cytologic findings of PDC.
Materials and Methods: We reviewed thyroid carcinomas operated on in Kuma
Hospital from January 2004to June 2008, and collected 16 PDC cases that received
aspiration cytology for the thyroid nodules. Diagnosis of PDC required the identification
of insular, trabecular or solid patterns in the majority of the tumor. Nine of 16 PDC
cases were poorly differentiated papillary carcinoma, and the remaining seven were
poorly differentiated follicular carcinoma. We examined Papanicolaou-stained cytologic
specimens of those cases.
Results: Thirteen cases were cytologically diagnosed as malignant, and PDC was
suspected in seven of them. The remaining three cases were reported as undetermined
or benign tumor, and follicular neoplasm was suspected. The smears were highly
cellular.
The tumor cells mainly arranged as trabecular or large solidnests.
Less-cohesive aggregation was observed in one-third cases. Intranuclear cytoplasmic
inclusion was seen in four of papillary type and one of follicular type. Six cases showed
mitotic figures. Papillary and follicular pattern, one-layered sheet, moderate to large
amount of colloid, ropy colloid, multinucleated giant cells that are seen in
well-differentiated papillary or follicular carcinoma were not seen in over 10% of cases.
- 58 -
Conclusions:
We
conclude
that
trabecular
arrangements,
large
solid
nests,
less-cohesive aggregation, and mitotic figures are the cytologic findings indicating PDC.
We emphasize that the arrangements of tumor cells is more important than cellular
findings on diagnosing PDC, except for mitotic figures.
- 59 -
【P-20】
Differential diagnosis between basal cell adenoma and
adenoid cystic carcinoma of salivary gland in cytologic
specimen.
Woong-Na, Se-Min Jang, Young-Jin Jun, Young-Ha Oh, Moon-Hyang Park
Department of pathology, Hanyang University College of medicine
In making surgical plan, preoperative differential diagnosis between basal cell
adenoma (BCA) and adenoid cystic carcinoma of salivary gland is challengeable and
problematic to pathologist and surgeon, because a patient with adenoid cystic carcinoma
needs wider margin resection, which can cause facial nerve paralysis. A number of
previous literatures suggested some cytologic features that could be useful for
differential diagnosis, such as amount of cytoplasm, hyaline globules, basement
membrane‐like stroma, arrangement, nuclear irregularity and chromatin pattern. But in
certain exceptional subtypes of tumor, some features could be confusing or even lead to
misdiagnosis. Recently, Hara et al tried to measure the sizes of tumor nuclei by image
analysis and suggested that less than 5.1 micrometer in average of epithelial nuclear
short diameter was thought to be the first criteria favoring BCA. Five cases of basal cell
adenoma and 5 cases of adenoid cystic carcinoma were reviewed and analyzed by
reported cytologic criteria. Two of five basal cell adenoma contained membranous
subtype. We reviewed the cases with by the useful 5 items for a cytological differential
diagnosis of BCA by classical point of view and technique of image analysis. We
concluded that the useful criteria were nuclear size, mild cellular atypia and cellular
cohesion in differential diagnosis between BCA and adenoid cystic carcinoma of salivary
gland.
- 60 -
【P-21】
A Case of Primary Small Cell Carcinoma of the Breast
1)
1)
1)
1)
Yumi Miyai(MD) , Yoshio Kushida(MD) , Toshitetsu Hayashi(MD) , Kyuichi Kadota(MD) ,
Naomi Katsuki(MD)1), Katsuyuki Noma(CT)2), Yoshihito Yano(CT)2), Masashi Ishikawa(MD)2),
3)
1)
Eiichiro Hirakawa(MD) , Reiji Haba(MD)
1)
Department of Diagnostic Pathology, University Hospital, Faculty of Medicine, Kagawa University
2)
Department of Pathology, Saiseikai Imabari Hospital
3)
Department of Medical Technology, Faculty of Health Sciences,
Kagawa Prefectural College of Health Sciences
Primary small cell carcinoma of the breast is an exceedingly rare variant of breast
carcinoma. Here, we report a case of primary small cell carcinoma of the breast.
A 82-year-old woman presented with a lump in her left breast. A physical
examination revealed a mass measuring about 2 cm in diameter in the lower inner
quadrant of her left breast. On fine-needle aspiration biopsy, the diagnosis of
malignancy (small cell carcinoma) was made, and the patient was treated with
mastectomy of the left breast with lymph node dissection.
Fine-needle aspiration biopsy revealed loosely arranged clusters of small cells,
together with dispersed single small cells with background necrosis and bleeding. The
tumor cells had scanty cytoplasm and round to oval nuclei with minimal nuclear
pleomorphism and variation in size. The nuclei werehyperchromatic, and chromatin was
fine and powdery. Nuclear molding and nuclear streaking of crush artifact were also
found. Based on these findings, we diagnosed small cell carcinoma.
Histological examination showed that most of the tumor consisted of small cells
having a high nucleocytoplasmic ratio. The tumor cells proliferated in nests or
trabecular patterns. The findings were similar to small cell carcinoma of the lung. Part
of the tumor, the intraductal component, was composed of small tumor cells, and
adenocarcinoma with glandular features was found. Immunohistochemically, the tumor
cells were almost entirely positive for NSE, and focally positive for chromogranin A and
synaptophysin.
In this case, the presence of a non-mammary primary site could be ruled out
clinically, and an in-situ component was found. From these findings, we diagnosed
primary small cell carcinoma of the breast.
The treatment and prognosis of primary small cell carcinoma of the breast are
thought to differ from those of common types of breast carcinoma. Therefore, it is
necessary to understand the characterization of this unusual breast tumor.
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List of the Japanese Participants
1. Atsuhiko Sakamoto, MD (Representative)
Department of Pathology, Kyorin University School of Medicine, Tokyo
2. Michiru Umino, CT
Department of Pathology, Kyorin University School of Medicine, Tokyo
3. Makoto Saito, CT
Division of Pathology, Kyorin University Hospital, Tokyo
4. Nozomi Iwamoto, CT
Division of Pathology, Kyorin University Hospital, Tokyo
5. Reiji Haba, MD
Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa
6. Yoshio Kushida, MD
Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa
7. Yumi Miyai, MD
Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa
8. Toshitetsu Hayashi, MD
Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa
9. Kazuko Hasegawa, CT
Shikoku Cytopathological Laboratory, Kagawa
10. Junko Tanizawa, CT
Shikoku Cytopathological Laboratory, Kagawa
11. Tatsuo Sawada, MD
Department of Pathology, Tokyo Women’s Medical University, Tokyo
12. Yuji Nonami, CT
Department of Surgical Pathology, Tokyo Women’s Medical University, Tokyo
13. Kiyotaka Wakui, CT
Department of Clinical Laboratory Pathology, Akiru Municipal Medical Center, Tokyo
14. Kiyomi Taniyama, MD
Institute for Clinical Research, NHO Kure Medical Centerand Chugoku Cancer Center,
Hiroshima
- 62 -
15. Akihisa Saito, DDS
Department of Diagnostic Pathology, NHO Kure Medical Center and Chugoku Cancer Center,
Hiroshima
16. Harue Tsugawa, CT
Department of Diagnostic Pathology, NHO Kure Medical Center and Chugoku Cancer Center,
Hiroshima
17. Yoko Ozaki, NT
Nurses’ School, National Hospital Organization Kure Medical Center, Hiroshima
18. Mayumi Okuda, NT
Nurses’ School, National Hospital Organization Kure Medical Center, Hiroshima
19. Shiori Ono, NS
Nurses’ School, National Hospital Organization Kure Medical Center, Hiroshima
20. Eri Kokunishi, NS
Nurses’ School, National Hospital Organization Kure Medical Center, Hiroshima
21. Tomoyo Kawaguchi, NS
Nurses’ School, National Hospital Organization Kure Medical Center, Hiroshima
22. Kanae Honkawa, NS
Nurses’ School, National Hospital Organization Kure Medical Center, Hiroshima
23. Atsuko Okamoto, CT
Department of Pathology, Hiroshima City Asa Hospital, Hiroshima
24. Mayumi Kaneko, MD
Department ofPathology, Hiroshima City Asa Hospital, Hiroshima
25. Shinobu Umemura, MD
Department of Pathology, Tokai University School of Medicine, Kanagawa
26. Sadayuki Hiroi, CT
Department of Pathology and Laboratory Medicine, National Defense Medical College,
Tokorozawa, Saitama
27. Mitsuyoshi Hirokawa, MD
Department of Pathology and Cytology, Kuma Hospital , Kobe
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■
Letter of Appreciation
On behalf of the Korean Society for Cytopathology, I would like to express our
sincere gratitude to the members of the Japanese Society of Diagnostic Cytology for
your attendance as well as for providing a generous fund (￥300,000) for the
successful The 7th Korea-Japan Joint Meeting of Diagnostic Cytopathology.
November 1, 2008
Chang Suk Kang, M.D. Ph.D.
President
The Korean Society for Cytopathology