Journal of Pathology and Translational Medicine

Case Study

Malignant potential of neuroendocrine microtumor of the pancreas harboring high-grade transformation: lesson learned from a patient with von Hippel-Lindau syndrome: Jongwon Lee, Kyung Jin Lee, Dae Wook Hwang, Seung-Mo Hong; J Pathol Transl Med. 2024;58(2):91-97. Published online March 13, 2024; DOI: https://doi.org/10.4132/jptm.2024.02.13

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Pancreatic neuroendocrine microtumor (PNEMT) is a neuroendocrine tumor (NET) < 0.5 cm in diameter, and it is considered benign. We report a PNEMT with high-grade transformation (HGT). A man in his 60s with von Hippel-Lindau syndrome underwent surgical resection of a NET. A second sub-centimeter nodule with a nodule-in-nodule pattern was discovered. The 0.4 cm outer nodule contained clear columnar cells with round nuclei and indistinct nucleoli, while the 0.1 cm inner nodule had eosinophilic cells with an increased nuclear to cytoplasmic ratio, vesicular nuclei, and prominent nucleoli. Tumor cells in the outer and inner nodules were synaptophysin and chromogranin positive. Only the inner nodule was p53 positive, while the outer nodule was exclusively positive for carbonic anhydrase 9 and vimentin. The Ki-67 labeling indices for the outer and inner nodules were 2.1% (grade 1) and 44.3% (grade 3), respectively. This nodule was determined to be a PNEMT with HGT. Our findings suggest that a PNEMT may not always be benign and can undergo HGT.

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Molecular Basis of Pancreatic Neuroendocrine Tumors
Alesia Maluchenko, Denis Maksimov, Zoia Antysheva, Julia Krupinova, Ekaterina Avsievich, Olga Glazova, Natalia Bodunova, Nikolay Karnaukhov, Ilia Feidorov, Diana Salimgereeva, Mark Voloshin, Pavel Volchkov
International Journal of Molecular Sciences.2024; 25(20): 11017. CrossRef

Review

Trouble-makers in cytologic interpretation of the uterine cervix: Eunah Shin, Jaeeun Yu, Soon Won Hong; J Pathol Transl Med. 2023;57(3):139-146. Published online May 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.25

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Abstract PDF

The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.

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Pitfalls in Gynecological Cytology: Review of the Common and Less Frequent Entities in Pap Test
Danijela Vrdoljak-Mozetič, Snježana Štemberger-Papić, Damjana Verša Ostojić, Roberta Rubeša, Marko Klarić, Senija Eminović
Acta Cytologica.2024; 68(3): 281. CrossRef
Cytological features of human papillomavirus‐infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2
Mitsuaki Okodo, Kaori Okayama, Koji Teruya, Ruku Shinohara, Shuichi Mizuno, Rei Settsu, Yasuyoshi Ishii, Masahiko Fujii, Hirokazu Kimura, Mizue Oda
Journal of Medical Virology.2023;[Epub] CrossRef

Original Article

Myoferlin Expression and Its Correlation with FIGO Histologic Grading in Early-Stage Endometrioid Carcinoma: Min Hye Kim, Dae Hyun Song, Gyung Hyuck Ko, Jeong Hee Lee, Dong Chul Kim, Jung Wook Yang, Hyang Im Lee, Hyo Jung An, Jong Sil Lee; J Pathol Transl Med. 2018;52(2):93-97. Published online March 14, 2018; DOI: https://doi.org/10.4132/jptm.2017.11.29

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Abstract PDF

Background
For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression.
Methods
We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens.
Results
Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p<.001).
Conclusions
Our study revealed that myoferlin loss is significantly correlated with high FIGO grade of endometrioid carcinoma.

Citations

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Hayley Fowler, Rachael E. Clifford, David Bowden, Paul A. Sutton, Naren Govindarajah, Matthew Fok, Mark Glenn, Michael Wall, Carlos Rubbi, Simon J.A. Buczacki, Amit Mandal, Hayley Francies, Jonathan Hughes, Jason L. Parsons, Dale Vimalachandran
International Journal of Radiation Oncology*Biology*Physics.2024; 120(4): 1111. CrossRef
Neoexpression of JUNO in Oral Tumors Is Accompanied with the Complete Suppression of Four Other Genes and Suggests the Application of New Biomarker Tools
Dominik Kraus, Simone Weider, Rainer Probstmeier, Jochen Winter
Journal of Personalized Medicine.2022; 12(3): 494. CrossRef
Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma
Ji Min Na, Dong Chul Kim, Dae Hyun Song, Hyo Jung An, Hyun Min Koh, Jeong-Hee Lee, Jong Sil Lee, Jung Wook Yang, Min Hye Kim
Journal of Pathology and Translational Medicine.2022; 56(4): 199. CrossRef
PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis
Tao Qian, Chengmin Liu, Yanyan Ding, Chen Guo, Renwei Cai, Xiaoxia Wang, Rong Wang, Kuo Zhang, Li Zhou, Yi Deng, Chuanyue Wu, Ying Sun
Oncogene.2020; 39(10): 2069. CrossRef
Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis
Gilles Rademaker, Brunella Costanza, Justine Bellier, Michael Herfs, Raphaël Peiffer, Ferman Agirman, Naïma Maloujahmoum, Yvette Habraken, Philippe Delvenne, Akeila Bellahcène, Vincent Castronovo, Olivier Peulen
Oncogenesis.2019;[Epub] CrossRef
Prognostic significance of immunohistochemical staining for myoferlin in clear cell renal cell carcinoma and its association with epidermal growth factor receptor expression
Minsun Jung, Cheol Lee, Jeong Hwan Park, Kyung Chul Moon
Urologic Oncology: Seminars and Original Investigations.2019; 37(11): 812.e9. CrossRef
Ferlin Overview: From Membrane to Cancer Biology
Olivier Peulen, Gilles Rademaker, Sandy Anania, Andrei Turtoi, Akeila Bellahcène, Vincent Castronovo
Cells.2019; 8(9): 954. CrossRef
Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers
Wei Zhu, Bolun Zhou, Chenxuan Zhao, Zhengqing Ba, Hongjuan Xu, Xuejun Yan, Weidong Liu, Bin Zhu, Lei Wang, Caiping Ren
Journal of Cellular and Molecular Medicine.2019; 23(11): 7180. CrossRef
Myoferlin, a Membrane Protein with Emerging Oncogenic Roles
Yimin Dong, Honglei Kang, Huiyong Liu, Jia Wang, Qian Guo, Chao Song, Yunlong Sun, Ya Zhang, Honghua Zhang, Zheng Zhang, Hanfeng Guan, Zhong Fang, Feng Li
BioMed Research International.2019; 2019: 1. CrossRef

Case Studies

Cytomorphological Findings and Histological Correlation of Low-Grade Cribriform Cystadenocarcinoma of Salivary Gland in Fine-Needle Aspiration: A Case Study: Young Sin Ko, Ja Seung Koo; Korean J Pathol. 2013;47(6):592-595. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.592

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Abstract PDF

Low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland is a rare tumor. We report the cytologic features and histologic correlation of a patient with LGCCC. A 57-year-old man had a hardly palpable, nontender mass in the right cheek area followed over nine months. Radiologic analysis revealed a 1.2 cm multiseptated, cystic, solid nodule in an anterior superficial lobe of the right parotid gland. Fine-needle aspiration cytology revealed many irregular overlapping sheets or clusters of ductal epithelial cells forming solid, pseudopapillary, and cribriform architectures. Nuclei of the tumor cells revealed inconspicuous atypia with minimal size variation. On the basis of these findings, we confirmed a diagnosis of ductal epithelial proliferative lesion, favoring neoplasm, with uncertain malignant potential. Tumor excision was performed, revealing a tiny multicystic nodule (0.7 cm). Histopathologically, this tumor showed the characteristic morphology of LGCCC. This is the first report of cytomorphological findings of LGCCC in Korea.

Citations

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Duct tales of a parotid gland swelling
Swati Raj, Monika Singh, Mamta Gupta, Naveen Thapliyal
Cytojournal.2023; 20: 22. CrossRef
Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification
Lester D.R. Thompson, Justin A. Bishop
Advances in Anatomic Pathology.2023; 30(2): 112. CrossRef
Intraductal carcinoma of the parotid gland
Yukiya HIRATA, Kayoko HIGUCHI, Toshitaka NAGAO, Yoko ZUKERAN, Takao KINJO, Naoki WADA
The Journal of the Japanese Society of Clinical Cytology.2022; 61(6): 431. CrossRef
Intraductal carcinomas of the salivary glands: systematic review and classification of 93 published cases
Andrea Palicelli
APMIS.2020; 128(3): 191. CrossRef
What do we know about the cytological features of pure intraductal carcinomas of the salivary glands?
Andrea Palicelli
Cytopathology.2020; 31(3): 185. CrossRef
Diagnosing Recently Defined and Uncommon Salivary Gland Lesions in Limited Cellularity Specimens: Cytomorphology and Ancillary Studies
Esther Diana Rossi, Zubair Baloch, William Faquin, Liron Pantanowitz
AJSP: Reviews and Reports.2020; 25(5): 210. CrossRef
Low-grade intraductal carcinoma of salivary glands: A systematic review of this rare entity
Francesco Giovacchini, Caterina Bensi, Stefano Belli, Maria Elena Laurenti, Martina Mandarano, Daniele Paradiso, Michele Giansanti, Antonio Tullio
Journal of Oral Biology and Craniofacial Research.2019; 9(1): 96. CrossRef
The rare entity of cystadenocarcinoma (CAC) in parotid gland: A single-center experience
Bing Guo, Yu-an Cao, Xingjun Qin, Chunyue Ma
Journal of Cranio-Maxillofacial Surgery.2019; 47(5): 826. CrossRef
Cytopathology approach to rare salivary gland lesions with oncocytic features
Siba El Hussein, Samer N. Khader
Diagnostic Cytopathology.2019; 47(10): 1090. CrossRef
Unicystic high‐grade intraductal carcinoma of the parotid gland: cytological and histological description with clinic–pathologic review of the literature
Andrea Palicelli, Paola Barbieri, Narciso Mariani, Paola Re, Stefania Galla, Raffaele Sorrentino, Francesca Locatelli, Nunzio Salfi, Guido Valente
APMIS.2018; 126(9): 771. CrossRef
Low-grade cribriform cystadenocarcinoma arising from a minor salivary gland: a case report
Masashi Kimura, Shinji Mii, Shinichi Sugimoto, Kosuke Saida, Shojiroh Morinaga, Masahiro Umemura
Journal of Oral Science.2016; 58(1): 145. CrossRef
A Case of Cystadenocarcinoma Arising from Parotid Gland
Jong Chul Hong, Tae Kyoung Koh, Min Gyoung Pak, Heon Soo Park
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2016; 59(4): 300. CrossRef
Mammary analogue secretory carcinoma of parotid gland
Atsuko NASU, Sakae HATA, Masaru FUJITA, Toyoko YAMAUCHI, Satoko NAKAMURA, Takehiro TANAKA, Kouichi ICHIMURA, Hiroyuki YANAI
The Journal of the Japanese Society of Clinical Cytology.2016; 55(2): 112. CrossRef

Fine-Needle Aspiration Cytology of Low-Grade Cribriform Cystadenocarcinoma with Many Psammoma Bodies of the Salivary Gland: Ji Yun Jeong, Dongbin Ahn, Ji Young Park; Korean J Pathol. 2013;47(5):481-485. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.481

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Abstract PDF

Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare salivary gland tumor that was recently defined as a variant of cystadenocarcinoma by the 2005 World Health Orgazniation (WHO) classification system. We report cytologic findings of an unusual case of LGCCC with many psammoma bodies. A 90-year-old man presented a palpable mass on his left parotid gland. Fine-needle aspiration (FNA) cytology showed tumor cells that were arranged in clusters and dispersed individually. The tumor cells showed mild atypia and had clear or dense cytoplasm with some vacuoles. Numerous psammoma bodies were noted. After surgical resection, the histologic examination revealed a mixed solid and cystic mass showing intraductal growth with focal stromal invasion. The S-100 protein expressed in the tumor cells, but smooth muscle actin and p63 were positive only in myoepithelial cells. Although LGCCCs resemble other salivary gland tumors, differentiating LGCCC during preoperative FNA is important to avoid unnecessary overtreatment.

Citations

Citations to this article as recorded by

Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification
Lester D.R. Thompson, Justin A. Bishop
Advances in Anatomic Pathology.2023; 30(2): 112. CrossRef
Duct tales of a parotid gland swelling
Swati Raj, Monika Singh, Mamta Gupta, Naveen Thapliyal
Cytojournal.2023; 20: 22. CrossRef
Intraductal carcinoma of the parotid gland
Yukiya HIRATA, Kayoko HIGUCHI, Toshitaka NAGAO, Yoko ZUKERAN, Takao KINJO, Naoki WADA
The Journal of the Japanese Society of Clinical Cytology.2022; 61(6): 431. CrossRef
Intraductal carcinoma of the retromolar trigone found with elevated serum CEA and CA19-9 levels: a case report
Mao KAWAKAMI, Nobuhiro UEDA, Yuka TAKAHASHI, Sho ARIKAWA, Nobuhiro YAMAKAWA, Tadaaki KIRITA
Japanese Journal of Oral and Maxillofacial Surgery.2021; 67(5): 292. CrossRef
Endoscopic trans‐pterygoid resection of a low‐grade cribriform cystadenocarcinoma of the infratemporal fossa
Vikram G. Ramjee, Landon J. Massoth, John P. Richards, Kibwei A. McKinney
World Journal of Otorhinolaryngology - Head and Neck Surgery.2020; 6(2): 115. CrossRef
Psammoma Bodies in a Large Myoepithelioma
Marcela Pessoa de Melo, Diego Filipe Bezerra Silva, Rodrigo Alves Ribeiro, Tony Santos Peixoto, Daliana Queiroga de Castro Gomes, Pollianna Muniz Alves, Cassiano Francisco Weege Nonaka, Bárbara Vanessa de Brito Monteiro
Journal of Craniofacial Surgery.2020; 31(4): e326. CrossRef
Low-grade intraductal carcinoma of salivary glands: A systematic review of this rare entity
Francesco Giovacchini, Caterina Bensi, Stefano Belli, Maria Elena Laurenti, Martina Mandarano, Daniele Paradiso, Michele Giansanti, Antonio Tullio
Journal of Oral Biology and Craniofacial Research.2019; 9(1): 96. CrossRef
What is your diagnosis? Submandibular mass in a dog
Julie Allen, Ashley M. Talley, Carol B. Grindem, Jennifer A. Neel
Veterinary Clinical Pathology.2018; 47(4): 676. CrossRef
Primary acinic cell carcinoma of the lung with psammoma bodies: A case report and review of literature
Xiu-Peng Zhang, Gui-Yang Jiang, Qing-Fu Zhang, Hong-Tao Xu, Qing-Chang Li, En-Hua Wang
Pathology - Research and Practice.2017; 213(4): 405. CrossRef
Cytology of low‐grade cribriform cystadenocarcinoma in salivary glands: Cytological and immunohistochemical distinctions from other salivary gland neoplasms
Yoshiki Ohta, Yuko Hirota, Yohko Kohno, Koji Kishimoto, Tomoko Norose, Nobuyuki Ohike, Masafumi Takimoto, Akira Shiokawa, Hidekazu Ota
Diagnostic Cytopathology.2016; 44(3): 241. CrossRef
Low-grade cribriform cystadenocarcinoma arising from a minor salivary gland: a case report
Masashi Kimura, Shinji Mii, Shinichi Sugimoto, Kosuke Saida, Shojiroh Morinaga, Masahiro Umemura
Journal of Oral Science.2016; 58(1): 145. CrossRef
A Case of Cystadenocarcinoma Arising from Parotid Gland
Jong Chul Hong, Tae Kyoung Koh, Min Gyoung Pak, Heon Soo Park
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2016; 59(4): 300. CrossRef

Original Articles

p53 Protein Expression in Infiltrating Ductal Carcinoma of the Breast.: Soon Hee Jung, Mee Yon Cho, Soo Yong Kim; Korean J Pathol. 1996;30(1):7-14.

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Abstract PDF: Overexpression of the nuclear phosphoprotein p53 is the most common genetic anomaly found in primary human cancer and mutation of the tumor suppressor gene p53 has been identified in breast cancer cell lines. In this study, we evaluated the prognostic significance of p53 protein expression in patients with mammary infiltrating ductal carcinoma and its correlation with histopathologic grade, lymph node status, tumor size, p53 protein expression and survival. Among 53 cases, p53 protein expression was detected in 26(49.1%) cases by immunohistochemistry. There was no correlation between p53 protein overexpression and histopathologic grade(p=0.09) or lymph node status(p=0.38) and between survival and histopathologic grade (p=0.68) or lymph node status(p=0.52). However, p53 protein expression was significantly correlated with survival(p=0.01) and patients with p53 protein-positive tumors showed poorer survival times. But Cox multivariate analysis showed the lymph node status is significant(p=0.01). The authors conclude that the presence of mutant p53 protein and lymph node status may serve a prognostic role, in a subset of mammary infiltrating ductal carcinoma cases.

Correlation between Nuclear Grades and the Numbers of AgNORs and PCNA Labeling Indices in Renal Cell Carcinoma.: Hye Jin Lee, Young Im Han, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1996;30(2):132-139.

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Abstract PDF: The author examined the number of AgNORs and PCNA labeling indices by histochemical and immunohistochemical studies in 20 cases of renal cell carcinoma, composed of 5 cases according to the nuclear grades. The results obtained are summarized as follows; 1) Mean number of AgNORs according to the nuclear grades of renal cell carcinoma were 1.38+/-0.40 (mean+/-standard deviation) for Grade I, 2.53+/-0.33 for Grade II, 5.43+/-0.66 for Grade III, and 7.88+/-0.72 for Grade IV. The mean numbers of AgNORs according to the nuclear grades were significantly increased(p=0.0005). 2) PCNA labeling indices (positive nuclear ratio) according to the nuclear grades of renal cell carcinoma were 5.90+/-2.36 for Grade I, 19.30+/-6.71 for Grade II, 45.73+/-8.62 for Grade III, and 61.83+/-6.34 for Grade IV. Also, the PCNA labeling indices according to the nuclear grades were significantly increased(p=0.0008). 3) The mean numbers of AgNORs directly correlated with the PCNA labeling indices (r=0.9861, p<0.001). On the basis of the above results, it was considered that the numbers of AgNORs and PCNA labeling indices as markers of proliferative activity of tumor cells correlate well with the nuclear grades of renal cell carcinoma.

Case Report

Papillary Neoplasm of the Endolymphatic Sac: A report of two cases.: Jai Hyang Go, Yoon Jung Choi, Tae Seung Kim, Chan Il Park; Korean J Pathol. 1996;30(2):150-154.

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Abstract PDF: Papillary tumor of the temporal bone or middle ear has been recognized as an aggressive neoplasm because of its invasive growth pattern. The site of origin is controversial so that most cases have been reported under various diagnostic terms. Recently, Heffner(1989) suggested that the endolymphatic sac is a possible site of origin, because the tumor resembles the endolymphatic sac in several aspects. We report two such cases. One patient was a 34-year-old female presenting with tinnitus and hearing difficulty for 1 year. Temporal bone CT revealed extensive bone destruction by the tumor which was located in the posterolateral aspect of temporal bone. The other patient was a 56-year-old female who complained of tinnitus, dizziness and otalgia for 2 years. Cranial MR imaging showed an irregularly marginated mass in the left jugular fossa with extension to the petrous bone. Histologically, both cases showed a papillary pattern and locally destructive growth that are typical of papillary tumor of the endolymphatic sac. The papillae were lined by a single layer of bland-looking cuboidal to low columnar cells. Immunohistochemically the lining cells expressed cytokeratin, epithelial membrane antigen, neuron specific antigen and in one case, S-100 protein, supporting the thesis that these neoplasms might be of endolymphatic sac origin.

Original Articles

Angiogenensis and Overexpression of p53 Gene Produc in Brain Tumor.: Jeong Yun Shim, Ho Guen Kim, Tai Seung Kim; Korean J Pathol. 1997;31(1):23-33.

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Abstract PDF: Angiogenesis depends on the net balance between positive and negative angiogenic factors. Tumor cells are angiogenic resulting from increased production of positive factors and decreased production of negative factors. Among these, vascular endothelial growth factor and glioma- derived angiogenesis inhibiting factor are related to glioblastoma multiforme. The p53 gene is more frequently mutated than any other known oncogene or tumor suppressor gene in human tumors including glioblastoma multiforme. Angiogenesis is reported to be controlled by p53 regulation in recent studies. To examine the effect of p53 overexpression on angiogenesis in glioblastoma multiforme, we performed immunohistochemical staining in 51 cases of glioblastoma multiforme, using monoclonal antibodies to p53 protein and factor VIII. 20 cases of low grade astrocytoma were used as control. p53 overexpression was present in 15(75%) of 20 cases of low grade astrocytoma and the mean vessel count was 37.7+/-9.9 at x200 field and 17.5+/-5.8 at x400 field. p53 overexpression was present in 35(68%) of 51 cases of glioblastoma multiforme and the mean vessel count was 91.9 45.8 at x200 field and 40.7 19.1 at x400 field. Mean vessel count in low grade astrocytoma with p53 overexpression was 39.4 10.2 at x200 field and 18.9 5.7 at x400 field, while in cases without p53 overexpression it was 32.4+/-7.6 at x200 field and 13.2 3.5 at x400 field. Mean vessel count in glioblastoma multiforme with p53 overexpression was 94.5+/-51.8 at x200 field and 42.1+/-16.8 at x400 field, while in cases without p53 overexpression it was 86.1+/-29.5 at x200 field and 37.1+/-16.8 at x400 field. The mean survival time was 12.4 months in the 39 cases of glioblastoma multiforme in which follow-up studies were possible. Significant prognostic factors were age, p53 overexpression and adjuvant therapy. These results show that p53 gene mutation is one of the many contributing factors to angiogenesis in glioblastoma multiforme. In addition, other oncogenes and tumor suppressor genes, as well as growth factors may be involved. Age, p53 overexpression and adjuvant therapy proved to be significant prognostic factors, while microvessel density was not.

Flow Cytometric DNA Analysis of Gastrointestinal Stromal Tumors .: Mee Yon Cho, Soon Won Hong, Soon Hee Jung, Hogeun Kim, Chanil Park; Korean J Pathol. 1997;31(7):608-616.

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Abstract PDF: To evaluate the correlation between the histologic grade and DNA ploidy or proliferation index/S phase fraction (SPF) of gastrointestinal stromal tumors, we performed the DNA analysis using the flow cytometry. Paraffin embedded tissue samples of 57 gastrointestinal stromal tumors were used. The sites of the tumors were: stomach (28), small intestine (23), and large intestine(6). DNA index, proliferative index, and SPF by the flow cytomery were compared with histologic grade. The histologic grade of the gastric tumors were benign (12), borderline (10), and malignant (6). Those of the small intestinal timors were benign (2), borderline (13), and malignant(8). The large intestine were borderline (2), and malignant (4). In stomach, aneuploidy was found in 25.0% of benign, 40.0% of borderline, and 100% of malignant. And there was statistically significant correlation between the histologic grade and ploidy (p < 0.05). By contrast, small and large intestinal tumors showed more frequent aneuploidy in benign than in malignant. The proliferative index was correlated with the histologic grade in gastric tumors (p<0.05), but the SPF was not. In conclusion, the ploidy and proliferative index of gastric tumors are closely correlated to the histologic grade. However, aneuploidy in tumors of the small and large intestine were difficult to predict the malignancy.

E-Cadherin Expression in Breast Carcinoma: Correlation with Tumor Grade and Hormone Receptor.: Haeng Ji Kang, Chan Pil Park, Chan Kum Park; Korean J Pathol. 1997;31(11):1172-1179.

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Abstract: E-cadherin (E-CD), a Ca2+ -dependent adhesion molecule, plays a major role in the maintenance of intercellular junctions in normal epithelial cells in most organs. Recently, a correlation has been observed between a loss of E-CD and increased invasiveness of neoplastic cells. In this study, E-CD expression in the breast carcinoma was investigated using monoclonal antibody, anti-E-CD by immunohistochemical method. Expression of E-CD were evaluated in 57 breast carcinomas and correlated with their tumor grade, lymph node involvement, and hormonal receptor status. Histological types included in this study were 54 invasive ductal carcinomas (IDCs) of otherwise not specified and 3 invasive lobular carcinomas. Cases of histologic grade I IDC were 6, grade II 30, and grade III 18. Of 54 IDCs 39 (72.2%) showed moderate to strong linear staining at the cell borders regardless of their histologic grade, status of lymph node metastasis, and status of hormone receptor. Staining intensity of E-CD was reduced in 54 cases (83%) of IDC when compared with that of normal or benign breast lesions (P<0.01). All seven cases of intraductal carcinoma, which were included in 54 IDCs showed one or two grade reduced expression of E-CD than that of infiltrative lesions. Three invasive lobular carcinomas showed strong (1 case), moderate (1 case), and negative reactivity (1 case). The data indicated that loss of E-CD expression is a crucial event in the development of breast carcinoma.

p53 Expression and Ki-67 Labeling Index in Brain Tumor with Special Reference to Tumor and Histologic Grade.: Duck Hwan Kim, Yeon Lim Suh, Dong Ik Shin, Hyung Jin Shin, Jong Hyun Kim; Korean J Pathol. 1998;32(2):81-87.

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Abstract PDF: Mutation in the p53 suppressor gene is the most common genetic alteration found in human cancers including primary brain tumors. Ki-67 labeling index(LI) is known to be a marker of proliferating activity. The purpose of this study was to verify whether an immunohistochemical expression of p53 antibody and Ki-67 LI could be related to different clinicopathologic parameters including histologic grade, size, invasiveness and recurrence of the brain tumors. Materials were based on the 147 surgically resected brain tumors during the last two years. Of the 147 brain tumors, there were 35 astrocytic tumors, 35 meningiomas, 10 oligodendrogliomas, 7 craniopharyngiomas, 5 dysembryoplastic neuroepithelial tumors, 4 medulloblastomas, 5 ependymomas, 23 pituitary adenomas, 9 schwannomas, and 14 other brain tumors. The p53 expression and Ki-67 LI were higher in malignant brain tumors including astrocytic tumors, medulloblastoma, PNET and gliosarcoma. The p53 positivity was correlated with histologic grades and tumor recurrence. The brain tumors with a high Ki-67 LI(>6%) also showed a close relationship to a higher histologic grading, radiological invasiveness and recurrence. There was no evident correlation with the age and tumor size with p53 expression and Ki-67 LI. These results suggest that p53 overexpression and high proliferation potential of the tumor cells are associated with the higher histologic grade and aggressive clinical course in the central nervous system tumors.

Histological Grading and Staging of Chronic Hepatitis Standardized Guideline Proposed by the Korean Study Group for the Pathology of Digestive Diseases .: Young Nyun Park, Ho guen Kim, Chae Yoon Chon, Jae Bok Park, Jin Hee Sohn, Seung Ha Yang, Eun Sil Yu, Mi Seon Lee, Ja June Jang, Hee Kyung Chang, Jong Jae Jeong, Dae Young Kang, Yong Il Kim, Chan Il Park; Korean J Pathol. 1999;33(5):337-346.

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Abstract PDF: The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) should be discontinued in favor of etiologic terminology. The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and for the stage of disease. Members of the Korean Study Group for the Pathology of Digestive Diseases reviewed 30 cases of chronic hepatitis and reached the following consensus: 1) The pathology report of the biopsy samples with features of chronic hepatitis should include the etiology, grade and stage. 2) Grade and stage should be semiquantitatively evaluated as none, minimal, mild, moderate and severe. 3) For grading, lobular activity and periportal activity should be evaluated, separately. 4) To avoid confusion with other grading systems, simple report using descriptive terms rather than numerical records is recommended in daily practice. Criteria for each grade and stage should be presented and discussed. Histologic grading and staging of chronic hepatitis by new standardized guidelines will give more information about the prognosis as well as the present status of hepatitis. The terms CAH, CPH and CLH may be used in parentheses to facilitate relearning.

Correlation of Clinical Stage and Presumptive Prognostic Factors in Renal Cell Carcinoma.: Jin Ye Yoo, Hye Jae Cho; Korean J Pathol. 1999;33(11):1061-1066.

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Abstract PDF: Renal cell carcinoma is the most common primary cancer of the kidney. The tumor stage is a reliable prognostic marker in renal cell carcinoma which is significantly associated with patient survival. But assessment of other prognostic factors has produced varying and often conflicting results. We reevaluated the significance of varied prognostic parameters in 33 cases of renal cell carcinoma; clinical stage, cell type, histologic pattern, DNA ploidy, Ki-67 labeling index, and bcl-2 oncoprotein expression. We could not statistically prove that DNA ploidy and bcl-2 expression were related to any examined parameters. Cell type was not related to clinical stage nor nuclear grade but there was a significant correlation (p=0.002) between cell type and histologic pattern. Nuclear grade (p=0.007) and Ki-67 labeling index (p=0.036) were significantly related to clinical stage, suggesting their value as complementary prognostic markers for renal cell carcinoma.

p27Kip1 Expression and Apoptotic Index in Prostatic Adenocarcinoma.: Eun Sook Nam, Duck Hwan Kim, Hyung Sik Shin, Young Euy Park, Dae Yul Yang; Korean J Pathol. 1999;33(12):1139-1145.

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Abstract PDF: p27kip1, a cyclin dependent kinase inhibitor, has been recognized as a negative regulator of cell cycle. To investigate the role of p27kip1 on progression of cancer and apoptotic pathway, we analyzed p27kip1 expression using immunohistochemical stain in 40 cases of prostatic adenocarcinoma and apoptotic index by TUNEL method in 30 cases of prostatic adenocarinoma. Both were correlated with Gleason grade and Gleason score. Loss of p27kip1 expression was more frequent in prostatic adenocarcinomas of higher score (Gleason score 7 to 10) (60.7%) than in those of lower score (Gleason score 4 to 6) (33.3%) (p<0.05). The value of mean apoptotic index of carcinoma was 1.13+/-0.26, 1.80+/-0.91, 2.06+/-0.79, and 2.12+/-0.82 in grade 2, 3, 4, and 5, respectively, and was positively correlated with grade of carcinoma (p<0.05). Mean apoptotic index of higher Gleason score (score 7 to 10; 2.05+/-0.63) was also significantly increased than in lower Gleason score (score 4 to 6; 1.34+/-0.39) (p<0.05). Mean apoptotic index in cases with and without p27kip1 expression was 1.92+/-0.86 and 1.89+/-0.81, respectively (p>0.05). These results suggest that loss of p27kip1 expression and increased apoptotic index may be the morphologic markers to predict the behavior of prostatic adenocaricnoma. The role of p27kip1 on apoptotic pathway seems to be meager in this study and needs further study.

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