Journal of Pathology and Translational Medicine

Original Articles

A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea: Ja Yeong Seo, Ji Hyun Park, Ju Yeon Pyo, Yoon Jin Cha, Chan Kwon Jung, Dong Eun Song, Jeong Ja Kwak, So Yeon Park, Hee Young Na, Jang-Hee Kim, Jae Yeon Seok, Hee Sung Kim, Soon Won Hong; J Pathol Transl Med. 2019;53(6):378-385. Published online October 21, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.18

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Background
In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC).
Methods
Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases.
Results
The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAF^V600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27).
Conclusions
The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.

Citations

Citations to this article as recorded by

Case report & review: Bilateral NIFTP harboring concomitant HRAS and KRAS mutation: Report of an unusual case and literature review
Marianna Rita Brogna, Francesca Collina, Maria Grazia Chiofalo, Debora De Bartolo, Angela Montone, Maria Rosaria Schiano, Michele Del Sesto, Nubia Pizza, Gerardo Ferrara
Molecular Carcinogenesis.2024;[Epub] CrossRef
Analysis of a pre-2017 follicular variant papillary thyroid carcinoma cohort reclassified as noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP): an 11-year retrospective single institution experience
Shaham Beg, Sana Irfan Khan, Isabella Cui, Theresa Scognamiglio, Rema Rao
Journal of the American Society of Cytopathology.2023; 12(2): 112. CrossRef
Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: What a Surgeon Should Know
Jabir Alharbi, Thamer Alraddadi, Haneen Sebeih, Mohammad A Alessa, Haddad H Alkaf, Ahmed Bahaj, Sherif K Abdelmonim
Cureus.2023;[Epub] CrossRef
NTRK Fusion in a Cohort of BRAF p. V600E Wild-Type Papillary Thyroid Carcinomas
Seung Eun Lee, Mi-Sook Lee, Heejin Bang, Mi Young Kim, Yoon-La Choi, Young Lyun Oh
Modern Pathology.2023; 36(8): 100180. CrossRef
A Comprehensive Study on the Diagnosis and Management of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features
Bayan A. Alzumaili, Lauren N. Krumeich, Reagan Collins, Timothy Kravchenko, Emad I. Ababneh, Adam S. Fisch, William C. Faquin, Vania Nosé, Maria Martinez-Lage, Gregory W. Randolph, Rajshri M. Gartland, Carrie C. Lubitz, Peter M. Sadow
Thyroid.2023; 33(5): 566. CrossRef
Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center
Paola Vignali, Agnese Proietti, Elisabetta Macerola, Anello Marcello Poma, Liborio Torregrossa, Clara Ugolini, Alessio Basolo, Antonio Matrone, Teresa Rago, Ferruccio Santini, Rossella Elisei, Gabriele Materazzi, Fulvio Basolo
Cancers.2022; 14(2): 420. CrossRef
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy
Hee Young Na, So Yeon Park
Journal of Pathology and Translational Medicine.2022; 56(6): 319. CrossRef
SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules : Follow-up: How and how long?
Sophie Leboulleux, Livia Lamartina, Emmanuelle Lecornet Sokol, Fabrice Menegaux, Laurence Leenhardt, Gilles Russ
Annales d'Endocrinologie.2022; 83(6): 407. CrossRef
Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice
Kennichi Kakudo
Cancers.2022; 14(3): 812. CrossRef
Clinicopathological parameters for predicting non-invasive follicular thyroid neoplasm with papillary features (NIFTP)
Eunju Jang, Kwangsoon Kim, Chan Kwon Jung, Ja Seong Bae, Jeong Soo Kim
Therapeutic Advances in Endocrinology and Metabolism.2021; 12: 204201882110005. CrossRef
The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification
Chanchal Rana, Huy Gia Vuong, Thu Quynh Nguyen, Hoang Cong Nguyen, Chan Kwon Jung, Kennichi Kakudo, Andrey Bychkov
Thyroid.2021;[Epub] CrossRef
The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy
Amandeep Singh, Jeehoon Ham, Joseph William Po, Navin Niles, Tara Roberts, Cheok Soon Lee
Cells.2021; 10(5): 1082. CrossRef
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: Reclassification and outcome study
David Cubero Rego, Hwajeong Lee, Anne Boguniewicz, Timothy A. Jennings
Annals of Diagnostic Pathology.2020; 44: 151439. CrossRef
Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: From Echography to Genetic Profile
Francesca Maletta, Enrico Costantino Falco, Alessandro Gambella, Jasna Metovic, Mauro Papotti
The Tohoku Journal of Experimental Medicine.2020; 252(3): 209. CrossRef

The Definition of Minimal Extrathyroid Extension in Thyroid Pathology by Analyzing Sizable Intra- and Extrathyroid Blood Vessels: Hyae Min Jeon, Beom Jin Lim, Hang-Seok Chang, SoonWon Hong; Korean J Pathol. 2012;46(6):548-553. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.548

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Abstract PDF

Background

To define the exact boundary of the intrathyroid and extrathyroid aspects of a gland when determining the extent of cancer invasion, we plan to clarify the definition of sizable vascular structures, which is one of the helpful histologic clues in determining a minimal extrathyroid extension. We hypothesized that arterial wall thicknesses in extrathyroid soft tissue would be significantly different from the arteries in the thyroid parenchyma.

Methods

Twenty cases of papillary carcinoma were selected. The numbers and wall thicknesses of the arteries and arterioles in intrathyroid and extrathyroid tissue were evaluated. The absence of nerve tissue in the thyroid gland was confirmed using the S-100 protein immunohistochemical stain.

Results

The comparison of the mean thicknesses of the total arteries between the extrathyroid and intrathyroid tissues in the retrospective study (26.88 µm vs. 15.07 µm, respectively) and the prospective study (35.24 µm vs. 16.52 µm, respectively) revealed significant differences (p=0.000). The greatest thickness of the intrathyroid arteries was 67.93 µm.

Conclusions

According to our results, the study showed that the extrathyroidal arteries were significantly thicker than the intrathyroidal arteries. We suggest that the sizable blood vessels of extrathyroidal arteries should be greater than 67.93 µm in thickness.

Citations

Citations to this article as recorded by

Invasion in thyroid cancer: Controversies and best practices
Michiya Nishino, Jack Jacob
Seminars in Diagnostic Pathology.2020; 37(5): 219. CrossRef
MiR-221/222 promote migration and invasion, and inhibit autophagy and apoptosis by modulating ATG10 in aggressive papillary thyroid carcinoma
Hao Shen, Zaikai Lin, Haiyan Shi, Lingling Wu, Baojin Ma, Hong Li, Baobing Yin, Jun Tang, Hongjin Yu, Xiaoxing Yin
3 Biotech.2020;[Epub] CrossRef
Minimal extrathyroidal extension affects the prognosis of differentiated thyroid cancer: Is there a need for change in the AJCC classification system?
Zeming Liu, Yihui Huang, Sichao Chen, Di Hu, Min Wang, Ling Zhou, Wei Zhou, Danyang Chen, Haifeng Feng, Wei Wei, Chao Zhang, Wen Zeng, Liang Guo, Scott M. Langevin
PLOS ONE.2019; 14(6): e0218171. CrossRef
miR-199a-3p downregulation in thyroid tissues is associated with invasion and metastasis of papillary thyroid carcinoma
Chengbiao Liu, Meiling Xing, Liping Wang, Kejun Zhang
British Journal of Biomedical Science.2017; 74(2): 90. CrossRef
Clinicopathological Significance of Minimal Extrathyroid Extension in Solitary Papillary Thyroid Carcinomas
Chang Gok Woo, Chang Ohk Sung, Yun Mi Choi, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Suck Joon Hong, Dong Eun Song
Annals of Surgical Oncology.2015; 22(S3): 728. CrossRef
Intraoperative Frozen Section for the Evaluation of Extrathyroidal Extension in Papillary Thyroid Cancer
Om Prakash Prajapati, A. K. Verma, M. Sabaretnam
World Journal of Surgery.2015; 39(7): 1855. CrossRef
Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence
Eunjung Lee, Wonkyung Jung, Jeong-Soo Woo, Jae Bok Lee, Bong Kyung Shin, Han Kyeom Kim, Aeree Kim, Baek-hui Kim
Korean Journal of Pathology.2014; 48(2): 117. CrossRef

CD56 and High Molecular Weight Cytokeratin as Diagnostic Markers of Papillary Thyroid Carcinoma.: Mi Kyung Shin, Jeong Won Kim, Young Su Ju; Korean J Pathol. 2011;45(5):477-484.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.477

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Abstract PDF

BACKGROUND
The incidence of papillary thyroid carcinoma (PTC) has been increasing recently and a precise diagnosis is essential for optimal treatment. Ancillary immunohistochemical stains are important for diagnosing some difficult cases.
METHODS
The dignostic value of CD56, high molecular weight cytokeratin (HMCK), galectin-3 (GAL3), and cytokeratin 19 (CK19) were evaluated to distinguish PTC from other benign thyroid lesions (BTL). We studied 23 cases of papillary thyroid overt carcinomas, 57 papillary thyroid microcarcinomas, five follicular adenomas, five cases of Hashimoto's thyroiditis, and 12 nodular hyperplasias.
RESULTS
The statistical analysis showed significantly different expressions of CD56, HMCK, GAL3, and CK19 in PTC vs other BTL. The diagnostic specificity of HMCK and CD56 (90.9% and 72.7%, respectively) was higher than that of GAL3 and CK19 (50.0% and 36.4%, respectively). However, the sensitivity of HMCK and CD56 detection (92.5% and 95.0%, respectively) was lower than that of GAL3 and CK19 (98.8% and 100.0%, respectively). The combined use of CD56, HMCK, GAL3, and CK19 showed 87.5% sensitivity, 100.0% specificity, and 100.0% positive predictive value in differentiating PTC from other BTL.
CONCLUSIONS
Although the differential diagnosis of thyroid follicular lesions are based on histological and cytomorphological criteria, CD56 and HMCK might be useful markers for diagnosing PTC.

Citations

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Diagnostic role of immunohistochemical markers CK19 and CD56 in thyroid neoplasms
Pallavi Priyadarshini, Manoj Kumar Patro, Prasanta Kumar Das
MGM Journal of Medical Sciences.2023; 10(2): 176. CrossRef
CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall
Uiju Cho, Yourha Kim, Sora Jeon, Chan Kwon Jung
Applied Immunohistochemistry & Molecular Morphology.2022; 30(5): 389. CrossRef
CD-56 IMMUNOREACTIVITY IN FOLLICULAR CELL DERIVED LESIONS OF THYROID
Elvin Merin Cherian, Priya P. V, Sankar S
Journal of Evolution of Medical and Dental Sciences.2018; 7(17): 2066. CrossRef
Diagnostic utility of CK19 and CD56 in the differentiation of thyroid papillary carcinoma from its mimics
Nehal S. Abouhashem, Suzan M. Talaat
Pathology - Research and Practice.2017; 213(5): 509. CrossRef
Use of CD56 and cyclin D1 in differentiating thyroid hyperplasia from papillary thyroid carcinoma
Maha E. Salama, Wael S. Ibrahim
Egyptian Journal of Pathology.2016; 36(1): 39. CrossRef
Defining the value of CD56, CK19, Galectin 3 and HBME-1 in diagnosis of follicular cell derived lesions of thyroid with systematic review of literature
Duško Dunđerović, Jasmina Marković Lipkovski, Ivan Boričic, Ivan Soldatović, Vesna Božic, Dubravka Cvejić, Svetislav Tatić
Diagnostic Pathology.2015;[Epub] CrossRef
Utility of immunohistochemical markers in differential diagnosis of follicular cell-derived thyroid lesions
HananAlSaeid Alshenawy
Journal of Microscopy and Ultrastructure.2014; 2(3): 127. CrossRef
Utility of Immunohistochemical Markers in Diagnosis of Follicular Cell Derived Thyroid Lesions
Hanan AlSaeid Alshenawy
Pathology & Oncology Research.2014; 20(4): 819. CrossRef
Potential diagnostic utility of CD56 and claudin-1 in papillary thyroid carcinoma and solitary follicular thyroid nodules
Rasha M. Abd El Atti, Lobna S. Shash
Journal of the Egyptian National Cancer Institute.2012; 24(4): 175. CrossRef

Cancer Subtypes of Breast Carcinoma with Micropapillary and Mucinous Component Based on Immunohistochemical Profile.: Sun Young Min, Eun Jung Jung, Hyesil Seol, In Ae Park; Korean J Pathol. 2011;45(2):125-131.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.125

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Abstract PDF

BACKGROUND
Micropapillary carcinoma (MPC) is known to have a worse prognosis than the other subtypes of breast cancer. Occasionally, MPC is observed in association with invasive ductal carcinoma not otherwise specified (IDC NOS), as well as mucinous carcinoma.
METHODS
We examined the immunohistochemical expression of an estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in 127 cases of surgically resected MPC or IDC NOS with MPC. Further, we classified these cases based on their immunohistochemical profile.
RESULTS
Among the IDC NOS with MPC cases, 47 were luminal A (62.7%), 10 were luminal B (13.3%), and 9 were HER2 (12.0%). The MPC cases included 4 luminal A (50.0%), 2 luminal B (25.0%) and 1 HER2 (12.5%) subtypes. Of the mucinous carcinomas with MPC, 4 were grouped as luminal A (57.1%), 1 as luminal B (14.3%), and 2 as HER2 (28.6%) subtypes. However, among the mucinous carcinomas, 33 were categorized as luminal A (89.2%), 3 as luminal B (8.1%), and 1 as HER2 (2.7%) subtype, indicating a low incidence of HER2 subtype as compared to the other subtypes.
CONCLUSIONS
The luminal B and HER2 subtypes were prevalent in carcinomas with MPC. This result explains the poor prognosis of breast carcinomas with an MPC pattern.

Citations

Citations to this article as recorded by

Investigation of Clinical Histopathologic Features and Metabolic Parameters of ¹⁸F-FDG PET/CT in Invasive Breast Carcinoma with a Micropapillary Component
Elife Akgün, Göksel Alçın, Esra Canan Kelten Talu, Tevfik Fikret Çermik, Tuçe Söylemez Akkurt, Ebru Şen, Esra Arslan
Molecular Imaging and Radionuclide Therapy.2023; 32(3): 221. CrossRef
Micropapillary Breast Carcinoma: From Molecular Pathogenesis to Prognosis
Georgios-Ioannis Verras, Levan Tchabashvili, Francesk Mulita, Ioanna Maria Grypari, Sofia Sourouni, Evangelia Panagodimou, Maria-Ioanna Argentou
Breast Cancer: Targets and Therapy.2022; Volume 14: 41. CrossRef
Micropapillary variant of mucinous breast carcinoma: A distinct subtype
Katrina Collins, Andrew Ricci
The Breast Journal.2018; 24(3): 339. CrossRef
Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma
Hyun-Jung Kim, Kyeongmee Park, Jung Yeon Kim, Guhyun Kang, Geumhee Gwak, Inseok Park
Journal of Pathology and Translational Medicine.2017; 51(4): 403. CrossRef

Case Report

Spontaneous Pneumothorax as an Initial Manifestation of Metastatic Papillary Thyroid Carcinoma.: Jong Im Lee, Jung Ran Kim, Soo Sung Kim; Korean J Pathol. 2009;43(1):83-87.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.83

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Abstract PDF: Spontaneous pneumothorax occurs in a variety of lung diseases. Primary or metastatic lung cancers are rare, but important causes of pneumothorax. We report here on a case of pulmonary metastasis of thyroid papillary carcinoma that initially presented as spontaneous pneumothorax. A 32-year-old male with no history of thyroid disease underwent wedge resection of the lung due to recurrent pneumothorax. Histologically, the pleura and subpleural lung parenchyma revealed several micronodular lesions and randomly scattered glandular structures with mild cytological atypia. The cells were characterized by their overlapped hypochromatic nuclei with longitudinal grooves and inconspicuous nucleoli. On the additional sections, we found a few intranuclear inclusions and colloid-like material in the follicular structures. The glandular cells were immunoreactive for thyroglobulin, TTF-1, CK 7 and HMW-CK and they were focally immunoreactive for EMA, but they were negative for S100, chromogranin and CEA. The Ki-67 labelling index was 4%. Neck ultrasonography revealed an ill-defined hypoechoic nodule in the left lobe of the thyroid. The diagnosis of conventional, classical papillary carcinoma was made by both the cytology and the total thyroidectomy specimen. Pathologists should conduct a through histologic examination for the patients with recurrent spontaneous pneumothorax to search for the underlying causes.

Original Articles

Flow Cytometric DNA Analysis in Papillary Carcinoma of Thyroid Gland: comparison with Ki-67 immunohistochemical staining.: Mee Joo, Hye Je Cho; Korean J Pathol. 1996;30(11):959-965.

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Abstract PDF: Nuclear DNA content was measured using a flow cytometric method to analyze 36 paraffin- embedded and 7 fresh tissues of 43 papillary carcinomas of thyroid gland. DNA aneuploidy was found in 3 cases(6.9%) and diploidy in 40 cases(93.1%). But there were no suggestive findings in clinical history, and cytological and morphological features for aneuploidy. In 40 diploid cases, S-phase fraction(SPF) were analyzed with regard to sex, age, tumor size, presence or absence of capsular invasion, lymph node involvement and ground glass nuclei. Among the multiple factors, only the tumor size, especially the larger sized-group(above 2cm in tumor diameter) was found to have a statistically significant higher SPF than the smaller sized-group (p<0.05). And high SPF groups relatively well corresponded to the high risk group. Thirty nine cases of papillary carcinoma have also been evaluated for proliferative activity with Ki-67 monoclonal antibody. The average Ki-67 labeling index was 0.36% in total cases, and that of the aneuploid cases was 0.73%, which was higher than that of the diploid cases(0.33%). So. We think that the low aneuploid rate and low Ki-67 labeling index relatively well represent the usual good clinical course of this tumor and the high SPF is a suggestive finding for a high risk group.

Proliferative Activity of Thyroid Lesions Evaluated by Mitotic Count and Proliferating Cell Nuclear Antigen (PCNA).: Hwa Sook Jeong, Geon Kook Lee, Hyung Geun Song, Ro hyun Sung; Korean J Pathol. 1997;31(12):1297-1307.

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Abstract PDF: To evaluate the clinical and histopathological significance of the proliferative activity in neoplastic and non-neoplastic thyroid lesions, we analyzed the mitotic count and the proliferating cell nuclear antigen labeling index (PCNA-LI) by immunohistochemistry as the proliferation- related markers. In this study included were surgically removed normal thyroid tissue (27 cases), adenomatous goiter (15 cases), Hashimoto's thyroiditis (5 cases), follicular adenoma (13 cases), follicular carcinoma (7 cases), papillary carcinoma (44 cases), poorly differentiated carcinoma (2 cases) and undifferentiated carcinoma (3 cases). The median PCNA-LI was 0 in normal thyroid tissue, 0.5 in adenomatous goiter, 6.2 in Hashimoto's thyroiditis, 1.2 in follicular adenoma, 4.8 in follicular carcinoma, 8.5 in papillary carcinoma, 60.8 in poorly differentiated carcinoma, and 55.2 in undifferentiated carcinoma (p=0.0001). Although PCNA-LI was exceptionally high in Hashimoto's thyroiditis, it was suggested that PCNA-LI could be used as a marker differentiating benign lesions from malignant neoplasm. Also, it could differentiate follicular adenoma from follicular carcinoma. Except clinical stage (p=0.0397), PCNA-LI was not related with sex, size, histologic subtype, and lymph node metastasis in papillary carcinoma. The presence of mitosis differentiated the neoplastic thyroid lesions from the non-neoplastic lesions (p<0.05), however, it could not divide benign and malignant neoplasm. These results suggest that an evaluation of the proliferative activity can help to differentiate the thyroid lesions. In addition, there was no significant correlation between the value of PCNA-LI and the presence of mitosis. It can be recommended to evaluate both the mitotic count and the PCNA-LI for determining the proliferative activity of the thyroid lesions.

Prognostic Significance of the Tall Cell Variant of Papillary Thyroid Carcinoma: Expression of p53, bcl-2 & Leu-M1 proteins.: Won Mi Lee, Joo Seob Keum, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(11):1000-1007.

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Abstract: Papillary carcinoma of the thyroid is a well differentiated neoplasm and usually has a good prognosis. However, a subset of morphologically distinct papillary carcinoma has bad prognoses. The tall cell variant of papillary carcinoma (TCPC), characterized by tall columnar cells with a height at least twice the width, is the one of these. In order to differentiate TCPC from usual papillary carcinoma (UPC) in terms of prognosis, we performed immunohistochemical studies for the expression of p53, bcl-2 and Leu-M1 proteins in 25 cases of TCPC, 26 cases of UPC and 14 cases of poorly differentiated, solid type papillary carcinoma (SPC) with an analysis of clinical parameters. The nuclear expression of p53 was noted in one case each of UPC and TCPC. The cytoplasmic p53 expression of TCPC, UPC, and SPC was observed in 17/25 cases (68%), 14/26 cases (54%), 3/14 cases (21%), respectively. bcl-2 expression was 19/25 cases (76%), 18/26 cases (69%), 5/14 cases (36%), and that of Leu-M1 was 21/25 cases (84%), 18/26 cases (69%), 4/14 cases(29%), respectively. There were no statistical significance in the expression of those immunoproteins among these three groups (p>0.05). The p53 protein was consistently expressed in the cytoplasm rather than nucleus in this study and was very well correlated to bcl-2 positivity (p<0.01). There were no statistical significance in any clinical parameters examined among these three groups (p>0.05). In conclusion, TCPC can not be separated from UPC as a distinct entity in this study and the cytoplasmic expression of p53 protein provides another mechanism of p53 inactivation in tumorigenesis of the thyroid papillary carcinoma, possibly by bcl-2 related mechanism.

Case Report

Invasive Micropapillary Carcinoma of the Breast: A clinicopathologic study of 16 cases.: Young Kyung Bae, Dong Sug Kim, Mi Jin Kim, Soo Jung Lee; Korean J Pathol. 1999;33(4):267-273.

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Abstract PDF: Invasive micropapillary carcinoma is a recently defined unusual variant of invasive breast carcinoma characterized by the formation of micropapillae within clear spaces separated by delicate fibrocollagenous stroma. This study was designed to examine clinicopathologic features of invasive micropapillary carcinoma of the breast. Sixteen cases of invasive micropapillary carcinoma were retrieved from the files of the Department of Pathology, Yeungnam University College of Medicine. We evaluated their clinicopathologic findings including patients' age, tumor size, nuclear grade, vascular invasion, axillary lymph node status, presence of extensive intraductal carcinoma, estrogen and progesterone receptors, p53, c-erbB-2, MIB-1 labelling index and follow-up data and compared this results with those of 292 cases of invasive ductal carcinoma, not otherwise specified. The incidence of invasive micropapillary carcinoma was 4.2% of all invasive breast carcinoma, and the mean age of the patients was 46 years. Nine cases were pure form (over 75% of micropapillary growth pattern in the tumor) and seven cases were mixed form. The results of clinicopathologic findings, except vascular invasion and axillary lymph node status, of the 16 cases of invasive micropapillary carcinoma were not different from those of the 292 cases of invasive ductal carcinoma, not otherwise specified (p>0.05). However, the rate of vascular invasion and axillary lymph node metastasis was significantly higher in invasive micropapillary carcinoma (p <0.05). Of 16 cases, five cases had distant metastasis during follow-up period, and one patient died of cancer. Although the mechanism of higher vascular invasion and lymph node metastasis in micropapillary growth pattern could not be determined, we propose that invasive micropapillary carcinoma should be recognized as a separate entity with increased risks of vascular invasion and axillary lymph node metastsis.

Original Articles

A study of Digital Image Analysis of Chromatin Texture for Discrimination of Thyroid Neoplastic Cells.: Sang Woo Juhng, Jae Hyuk Lee, Eun Kyung Bum, Chang Won Kim; Korean J Cytopathol. 1996;7(1):23-30.

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Abstract PDF: Chromatin texture, which partly reflects nuclear organization, is evolving as an important parameter indicating cell activation or transformation. In this study, chromatin pattern was evaluated by image analysis of the electron micrographs of follicular and papillary carcinoma cells of the thyroid gland and tested for discrimination of the two neoplasms. Digital grey images were converted from the electron micrographs; nuclear images, excluding nucleolus and intranuclear cytoplasmic inclusions, were obtained by segmentation; grey levels were standardized; and grey level histograms were generated. The histograms in follicular carcinoma showed Gaussian or near-Gaussian distribution and had a single peak, whereas those in papillary carcinoma had two peaks(bimodal), one at the black zone and the other at the white zone. In papillary carcinoma. the peak in the black zone represented an increased amount of heterochromatin particles and that at the white zone represented decreased electron density of euchromatin or nuclear matrix. These results indicate that the nuclei of follicular and papillary carcinoma cells differ intheir chromatin pattern and the difference may be due to decondensed chromatin and/or matrix substances.

Oxyphilic Papillary Carcinoma of the Thyroid in Fine Needle Aspiration .: Young Min Kim, Gyung Yub Gong, On Ja Kim; Korean J Cytopathol. 1997;8(1):52-56.

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Abstract PDF: Oxyphilic (H rthle) cells have abundant eosinophilic granular cytoplasms and occur in both benign and malignant neoplasms of the thyroid gland. Most published studies described mainly oxyphilic tumors of follicular type, and reports on oxyphilic papillary thyroid carcinomas are rare. The oxyphilic variant of papillary carcinoma differs from the classic papillary carcinoma in its more aggressive biological behavior. We report a case of oxyphilic papillary carcinoma exhibiting exclusively oxyphilic cells in a follicular pattern without papillary structures. The pattern of papillary carcinoma was confirmed by fine needle aspiration material and lymph nodal metastasis, both of which revealed typicaled papillary structures with characteristic nuclear features, psammoma bodies, and oxyphilic cytoplasm.

Fine Needle Aspiration Cytology of Intracystic Papillary Carcinoma of the Breast.: Ah Won Lee, Yeong Jin Choi, Kyo Young Lee, Byung Kee Kim, Sun Moo Kim, Sang In Shim; Korean J Cytopathol. 1997;8(2):179-184.

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Abstract PDF: Intracystic papillary carcinoma(IPC) of the breast is a distinctive and very rare variant of intrductal carcinoma. The cytologic features of IPC have been rarely reported, and there are difficulties in distinguishing between benign and malignant papillary breast lesions. Herein we report a IPC of the breast in a 80 year-old female. Fine needle aspiration cytology revealed monotonous cuboidal epithelial cells in small clusters and individually scattered on bloody background. The tumor cells did not show overt cytologic atypia. With the histologic features of this case and review of the literature, the cytologic differential points are discussed.

A Cytomorphologic Study of Benign and Malignant Papillary Neoplasms of the Breast.: Ho Jung Lee, Gyungyub Gong, Bohng Hee Kim, Sei Hyun Ahn, Jeong Mi Park, Jooryung Huh, Shin Kwang Khang, Jae Y Ro; Korean J Cytopathol. 1999;10(1):27-34.

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Abstract PDF: Benign and malignant papillary neoplasms of the breast may be difficult to distinguish in both cytologic and histologic preparations. To define the cytologic features of benign and malignant papillary lesions, we retrospectively reviewed 18 cases of fine needle aspirates from histologically confirmed cases of papilloma or papillary carcinoma of the breast. This study included 3 intraductal papillary carci nomas, 3 invasive papillary carcinomas, and 12 intraductal papillomas. All cases were evaluated for presence or absence of papillary fragments, bloody background, apocrine metaplasia, macrophages, and degree of cellularity, atypia, and single isolated columnar epithelial cells. Papillary fragments were present in all cases. The background of the smear was bloody in all 6 carcinomas, but in only 7 out of 12 papillomas. Markedly increased cellularity was present in 4 carcinomas(67%) and 7 papillomas(58%). Single cells were present in 5 carcinomas(83%) and 8 papil lomas(67%). The majority of papillomas and papillary carcinomas had mild to moderate atypia, and severe atypia was noted in one case of intraductal papillary carcinoma and one case of invasive papillary carcinoma. Apocrine metaplasia was absent in all cases of papillary carcinomas, but present in 8 papillomas(67%). Macrophages were noted in 4 carcinomas and were present in all cases of papillomas. The constellation of severe atypia, bloody background, absence of apocrine metaplasia and/or macrophages were features to favor carcinoma. Malignant lesions tended to show higher cellularity and more single isolated cells. The cytologic features mentioned above would be helpful to distinguish benign from malignant papillary lesions of the breast. However, because of overlapping of cytologic features, surgical excision should be warranted in all cases of papillary lesions of the breast to further characterize the tumor.

Case Report

Fine Needle Aspiration Cytology of Columnar Cell Variant of Papillary Carcinoma of the Thyroid: A Case Report .: Ji Han Jung, Kyo Young Lee, Chang Suk Kang, Sang In Shim, Byung Kee Kim; Korean J Cytopathol. 1999;10(2):179-184.

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Abstract PDF: The columnar cell variant of papillary carcinoma is a rare tumor of the thyroid, associated with aggressive behavior, early metastasis, and a rapidly fatal course. We present the fine needle aspiration cytologic(FNAC) findings of columnar cell variant of papillary carcinoma with cytohistologic correlation. In the smears, the tumor fragments showed mainly papillary pattern and a few scattered individual cells were present around the papillary fragments. The tumor cells were columnar or cuboidal and exhibited pseudostratification of the nuclei. The nuclei were oval to elongated with finely stippled chromatin and inconspicous nucleoli. Neither nuclear grooves nor intracytoplasmic inclusion was found. The FNAC diagnosis was consistent with papillary carcinoma. Total thyroidectomy was done and the histologic finding of the mass showed a predominantly papillary and focal solid proliferation of columar cells with marked nuclear pseudostratification. The unique histopathologic features and highly aggressive nature of columnar cell variant of papillary carcinoma require that this variant should be differeniated from common papillary carcinoma of the thyroid.

Original Article

Fine Needle Aspiration Cytology of Diffuse Sclerosing Variant of Papillary Carcinoma of the Thyroid: A Case Report.: Joon Mee Kim, Soo Kee Min, Young Chae Chu, Mi Rim Kim, Kyung Rae Kim; Korean J Cytopathol. 2000;11(1):47-52.

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Abstract PDF: Diffuse sclerosing papillary carcinoma(DSPC), a variant of papillary carcinoma of the thyroid, is characterized by diffuse involvement of one or both thyroid lobes, and histologic features such as prominent sclerosis, intense lymphocytic infiltrate, num erous psammoma bodies, and squamous metaplasia together with the charac teristic cytoarchitectural pattern of classical papillary carcinoma. We experienced a case of fine needle aspiration cytologic(FNAC) findings of DSPC, which was con firmed by histologic examination of the thyroidectomy specimens. The patient was 26 years old female who presented with diffuse firm enlargement of the thyroid gland with enlargement of many cervical lymph nodes. FNAC smears showed numerous psammoma bodies, many lymphocytes, metaplastic squamous cells, absence of stringy colloid, and epithelial cells showing classical features of papillary carcinoma, such as nuclear grooves, intranuclear inclusions, and ground glass chromatin pattern.

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