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Nuclear Morphological Changes in Papillary Thyroid Carcinoma Cell: The Utility of a 3-Dimensional (3D) Holographic Microscopy in Cytology Shoko Kure *1,2 , Mitsuhiro Kudo 1 , Kousuke Ishino 1 , Ryuichi Wada 1,2 and Zenya Naito 1,2 1 Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan 2 Department of Pathology, Nippon Medical School Hospital, Tokyo, Japan * Corresponding author: Shoko Kure, Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan, Tel: +81-3-3822-2131; E-mail: [email protected] Received date: December 05, 2018; Accepted date: December 12, 2018; Published date: December 18, 2018 Copyright: © 2018 Kure S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Image Article Fine needle aspiration cytology (FNAC) is an essential method to diagnose thyroid nodules. To diagnose papillary thyroid carcinoma (Figure 1a), distinct nuclear morphological changes such as nuclear groove (Figure 1b) and pseudo-nuclear inclusion (Figure 1c) are crucial features. At times, findings by FNAC with conventional cytology and findings by liquid-based cytology method are ambiguous. Subsequently, re-biopsy or even diagnostic resection is required. Additional or alternative methods to FNAC would be advantageous in diagnosing thyroid nodules. Optical diffraction tomography (ODT) microscopy (HT-2H, Tomocube Inc., Daejeon, Korea) is a 3D-holographic microscope to scan cells in three dimensions. is microscope has 110 nm lateral and 356 nm axial optical resolution. Image reconstruction is performed according to the reflection index and the thickness of the samples, which provides morphological information. Using the objective lenses with a magnification of 60x, nuclear, nucleoli, and lipid droplets, and other cytoplasmic organelles can be observed, similar to confocal laser microscopy. KTC-1 is a human papillary thyroid carcinoma cell-line, established from the malignant pleural effusion of a recurrent thyroid carcinoma patient. Detection of morphological changes of nuclear of KTC-1 cells by the phase-contrast microscope is not possible by conventional monolayer culture. Hence, formalin-fixed KTC-1 cells were stained with 4',6-diamidino-2-phenylindole (DAPI) and observed by HT-2H. Figure 1: Representative histology and cytology of thyroid papillary carcinoma. (a) Follicular cells proliferation, comprised of papillary structure in H&E staining. (b,c) Distinct nuclear features in FNAC samples in Papanicolaou staining; Arrows indicate nuclear grooves (b), and arrowheads pseudo-nuclear inclusions (c). e hollow, irregular nuclear shapes of KTC-1 cells were clearly detected (Figure 2). ese shapes indicate a nuclear groove and pseudo nuclear inclusion. us, observation and detection of nuclear morphological changes using whole cell images of FNAC nodule samples in 3D may be possible. ODT successfully captured nuclear morphological changes. Use of 3D-holographic microscopes may provide an alternative method or provide additional information for thyroid nodule diagnosis in cytology. J o u r n a l o f C yt o l o g y & H i s t o l o g y ISSN: 2157-7099 Journal of Cytology & Histology Kure, et al., J Cytol Histol 2018, 9:6 DOI: 10.4172/2157-7099.1000527 Image Article Open Access J Cytol Histol, an open access journal ISSN: 2157-7099 Volume 9 • Issue 6 • 1000527

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Page 1: yt o log is u r n tolog Journal of Cytology & Histology y ... · Journal of Cytology & Histology Kure, et al., J Cytol Histol 2018, 9:6 DOI: 10.4172/2157-7099.1000527 Image Article

Nuclear Morphological Changes in Papillary Thyroid Carcinoma Cell: TheUtility of a 3-Dimensional (3D) Holographic Microscopy in CytologyShoko Kure*1,2, Mitsuhiro Kudo1, Kousuke Ishino1, Ryuichi Wada1,2 and Zenya Naito1,2

1Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan2Department of Pathology, Nippon Medical School Hospital, Tokyo, Japan*Corresponding author: Shoko Kure, Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan, Tel: +81-3-3822-2131; E-mail: [email protected]

Received date: December 05, 2018; Accepted date: December 12, 2018; Published date: December 18, 2018

Copyright: © 2018 Kure S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited.

Image ArticleFine needle aspiration cytology (FNAC) is an essential method to

diagnose thyroid nodules. To diagnose papillary thyroid carcinoma(Figure 1a), distinct nuclear morphological changes such as nucleargroove (Figure 1b) and pseudo-nuclear inclusion (Figure 1c) arecrucial features. At times, findings by FNAC with conventionalcytology and findings by liquid-based cytology method are ambiguous.Subsequently, re-biopsy or even diagnostic resection is required.Additional or alternative methods to FNAC would be advantageous indiagnosing thyroid nodules.

Optical diffraction tomography (ODT) microscopy (HT-2H,Tomocube Inc., Daejeon, Korea) is a 3D-holographic microscope to

scan cells in three dimensions. This microscope has 110 nm lateral and356 nm axial optical resolution. Image reconstruction is performedaccording to the reflection index and the thickness of the samples,which provides morphological information. Using the objective lenseswith a magnification of 60x, nuclear, nucleoli, and lipid droplets, andother cytoplasmic organelles can be observed, similar to confocal lasermicroscopy. KTC-1 is a human papillary thyroid carcinoma cell-line,established from the malignant pleural effusion of a recurrent thyroidcarcinoma patient. Detection of morphological changes of nuclear ofKTC-1 cells by the phase-contrast microscope is not possible byconventional monolayer culture. Hence, formalin-fixed KTC-1 cellswere stained with 4',6-diamidino-2-phenylindole (DAPI) and observedby HT-2H.

Figure 1: Representative histology and cytology of thyroid papillary carcinoma. (a) Follicular cells proliferation, comprised of papillarystructure in H&E staining. (b,c) Distinct nuclear features in FNAC samples in Papanicolaou staining; Arrows indicate nuclear grooves (b), andarrowheads pseudo-nuclear inclusions (c).

The hollow, irregular nuclear shapes of KTC-1 cells were clearlydetected (Figure 2). These shapes indicate a nuclear groove and pseudonuclear inclusion. Thus, observation and detection of nuclearmorphological changes using whole cell images of FNAC nodule

samples in 3D may be possible. ODT successfully captured nuclearmorphological changes. Use of 3D-holographic microscopes mayprovide an alternative method or provide additional information forthyroid nodule diagnosis in cytology.

Jour

nal o

f Cytology &Histology

ISSN: 2157-7099

Journal of Cytology & HistologyKure, et al., J Cytol Histol 2018, 9:6DOI: 10.4172/2157-7099.1000527

Image Article Open Access

J Cytol Histol, an open access journalISSN: 2157-7099

Volume 9 • Issue 6 • 1000527

Page 2: yt o log is u r n tolog Journal of Cytology & Histology y ... · Journal of Cytology & Histology Kure, et al., J Cytol Histol 2018, 9:6 DOI: 10.4172/2157-7099.1000527 Image Article

Figure 2: KTC-1 cells observed by 3D-holographic microscope. Dot-lines outline a single cell. Arrows indicate the hollow and irregular shapeof the nucleus.

AcknowledgementThis work is supported by the Japanese Association of University

Women and Children’s Cancer Association of Japan. The authors thankDr. Norisato Mitsutake, Nagasaki University, for providing KTC-1 cell-

lines, and LMS Co., Ltd. Scientific Instruments Div., Kiyoko Kawahara,Takenori Fujii, Kiyoshi Teduka, Yoko Kawamoto and Taeko Kitamurafor their skillful assistance.

Citation: Kure S, Kudo M, Ishino K, Wada R, Naito Z (2018) Nuclear Morphological Changes in Papillary Thyroid Carcinoma Cell: The Utility of a3-Dimensional (3D) Holographic Microscopy in Cytology. J Cytol Histol 9: 527. doi:10.4172/2157-7099.1000527

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J Cytol Histol, an open access journalISSN: 2157-7099

Volume 9 • Issue 6 • 1000527