Journal of Pathology and Translational Medicine

Original Article

Elevated expression of Axin2 in intestinal metaplasia and gastric cancers: Dong Hui Lee, In Ho Jeong, Bogun Jang; J Pathol Transl Med. 2023;57(6):315-322. Published online November 7, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.12

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Background
The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly β-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in β-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies.
Methods
Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and β-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined.
Results
Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear β-catenin in gastric carcinomas (p < .001).
Conclusions
Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear β-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/β-catenin signaling pathway.

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Refining NTRK Fusion Detection in Papillary Thyroid Carcinoma Through Pan-TRK Immunohistochemistry and Histopathologic Features
Hyun Lee, Sue Youn Kim, Ji Min Park, Seung-Hyun Jung, Ozgur Mete, Chan Kwon Jung
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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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Case Studies

Squamous Metaplasia in Pleomorphic Adenoma: A Diagnostic and Prognostic Enigma: Swati Sharma, Monica Mehendiratta, Nivedita Chaudhary, Vineet Gupta, Maulshree Kohli, Anjana Arora; J Pathol Transl Med. 2018;52(6):411-415. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.15

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Abstract PDF

Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Histologically, squamous metaplasia has been reported in PA, but has rarely been documented as being extensive enough to cause significant misdiagnosis. Here, we present an unusual case of PA in a 50-year-old female patient presenting with swelling on the postero-lateral aspect of the palate for a week. Histopathologically, the tumor exhibited the features of conventional PA with extensive squamous metaplasia and giant keratotic lamellae in cyst-like areas. Such exuberant squamous metaplasia and keratin can be a diagnostic and prognostic pitfall and lead to overtreatment of the patient.

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ECTOPIC PLEOMORPHIC ADENOMA OF BUCCAL SPACE: CASE REPORT WITH REVIEW OF LITERATURE
SANCHIT BAJPAI
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Mahadevi B. Hosur, Rudrayya S. Puranik, Satyajit G. Dandagi, Vivekanand M. Patil
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CV Aiswarya, Raghunath Vandana, Kamal Firoz, Meda Samatha
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Anu Singh, Ravi Hari Phulware, Arvind Ahuja, Ankur Gupta, Manju Kaushal
Indian Journal of Otolaryngology and Head & Neck Surgery.2022; 74(S2): 2132. CrossRef
Aspiration cytology of pleomorphic adenoma with squamous metaplasia: A case series and literature review illustrating diagnostic challenges
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Salivary Gland Pleomorphic Adenomas Presenting With Extremely Varied Clinical Courses. A Single Institution Case-Control Study†
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Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia: Hyo Jeong Kang, Hui Jeong Jeong, So-Woon Kim, Eunsil Yu, Young-Joo Lee, So Yeon Kim, Jihun Kim; J Pathol Transl Med. 2018;52(4):226-231. Published online December 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.12

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Abstract PDF

Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.

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Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
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Original Article

Usual Interstitial Pneumonia with Lung Cancer: Clinicopathological Analysis of 43 Cases: Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Kyeongman Jeon, Man Pyo Chung, Jhingook Kim, Joungho Han; Korean J Pathol. 2014;48(1):10-16. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.10

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Abstract PDF

Background

Previous studies have suggested an association between usual interstitial pneumonia (UIP) and lung cancer (Ca). However, clinical and histological information is not enough to determine such an association, due to the low incidence and short survival time of patients with both conditions.

Methods

We retrospectively reviewed the clinical and histological records of Ca patients with UIP between January 1999 and August 2013 at the Samsung Medical Center, Seoul, Korea. We found 43 patients who had Ca with UIP (UIP-Ca). Previously reported data of eighty-four patients with UIP-only were included as a comparison group.

Results

Smoking is related to poor prognosis in patients with UIP-Ca, and the number of patients with a high smoking index of more than 30 pack-years significantly increased in UIP-Ca patients compared with UIP-only patients. There is no significant prognostic differentiation between UIP-Ca patients and UIP-only patients. Microscopically, UIP-Ca patients showed characteristically heterogeneous histological patterns and degrees of differentiation. There were many foci of squamous metaplasia or dysplasia at the peripheral area of squamous cell carcinomas.

Conclusions

We report 43 cases of UIP-Ca. Our results suggest that smoking is related to cancer occurrence in UIP patients and poor prognosis in UIP-Ca patients.

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Case Study

Peripheral Primitive Neuroectodermal Tumor with Osseous Component of the Small Bowel Mesentery: A Case Study: Joon Mee Kim, Young Chae Chu, Chang Hwan Choi, Lucia Kim, Suk Jin Choi, In Suh Park, Jee Young Han, Kyung Rae Kim, Yoon-La Choi, Taeeun Kim; Korean J Pathol. 2013;47(1):77-81. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.77

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Abstract PDF

A case of peripheral primitive neuroectodermal tumor of the small bowel mesentery with osseous component is reported. A 23-year-old man was admitted to our hospital because of acute severe abdominal pain. Abdominal computed tomography revealed a large solid and cystic, oval shaped mass, measuring 11.0×6.0 cm in the pelvic cavity. Histologically the resected lesion consisted of sheets of undifferentiated small round cells forming Homer-Wright rosettes and perivascular pseudorosettes, and showed areas of osteoid and bone formation. Immunohistochemical studies revealed that tumor cells expressed positivity against CD99 (MIC2), CD57, neuron-specific enolase, and vimentin. Fluorescence in situ hybridization study revealed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement on chromosome 22q12. To the authors' knowledge this is the first documentation of a peripheral neuroectodermal tumor with osteoid and bone formation of the small bowel mesentery.

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Case Reports

Melanotic Oncocytic Metaplasia of the Nasopharynx: A Report of Three Cases and Review of the Literature: Joo Young Na, Yeong Hui Kim, Yoo Duk Choi, Ji Shin Lee; Korean J Pathol. 2012;46(2):201-204. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.201

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Abstract PDF

Melanotic oncocytic metaplasia of the nasopharynx is a rare condition which is characterized by the presence of usually a small, brown to black colored pigmented lesion around the Eustachian tube opening. Although it is a benign lesion, it may be clinically misdiagnosed as malignant melanoma. Microscopically, melanotic oncocytic metaplasia is a combination of oncocytic metaplasia of the epithelium of the gland and melanin pigmentation in its cytoplasm. In our present study, we report three cases of melanotic oncocytic metaplasia of the nasopharynx. All the three cases occurred in men and were presented as multiple black pigmented lesions around the torus tubarius. Microscopically, mucous glands with diffuse oncocytic metaplasia and numerous black pigments were observed. No cellular atypia was observed. Immunohistochemically, the scattering of S-100 protein-positive, and human melanoma black 45-negative dendritic melanocytes was evident. This is the first report of cases of melanotic oncocytic metaplasia of the nasopharynx in Korea.

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Keiichiro Uehara, Yu Usami, Yukihiro Imai, Michio Shimizu
Pathology International.2015; 65(3): 144. CrossRef

Metaplastic Thymoma: Report of 4 Cases: Guhyun Kang, Nara Yoon, Joungho Han, Young Eun Kim, Tae Sung Kim, Kwhanmien Kim; Korean J Pathol. 2012;46(1):92-95. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.92

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Abstract PDF

Metaplastic thymoma (MT), accepted in the World Health Organization 2004 scheme, is a circumscribed tumor of the thymus exhibiting biphasic morphology. We herein describe the clinicopathologic features of four MTs and the differential diagnoses of this unusual tumor. There were three women and one man with mean age of 49.5 years. The patients were found to have mediastinal masses, and underwent surgical excision. One exhibited symptoms of myasthenia gravis, and the serum titer for anti-acetylcholine receptor antibody was positive. Grossly, the tumors were encapsulated, and showed vaguely multinodular, solid, tan-white to yellow cut surfaces. Histologically, they comprised epithelial islands intertwining with bundles of delicate spindle cells. The patients remained well after surgical excision at 5-55 months. Because of the distinctive histological appearance and benign clinical course, MT should be distinguished from other more aggressive mediastinal neoplasms displaying biphasic feature.

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Metaplastic thymoma: Report of two cases
Yoshikazu Shinohara, Mariko Tanaka, Kentaro Kitano, Kazuhiro Nagayama, Masaaki Sato, Jun Nakajima
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Type AB thymoma is not a mixed tumor of type A and type B thymomas, but a distinct type of thymoma
Yukari Miki, Kana Hamada, Tadashi Yoshino, Katsuya Miyatani, Kiyoshi Takahashi
Virchows Archiv.2014; 464(6): 725. CrossRef
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Jae Myoung Noh, Sang Yun Ha, Yong Chan Ahn, Dongryul Oh, Seung Won Seol, Young Lyun Oh, Joungho Han
Cancer Research and Treatment.2014; 47(3): 436. CrossRef
A Case of Metaplastic Thymoma
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Review

CpG Island Hypermethylation in Gastric Carcinoma and Its Premalignant Lesions: Gyeong Hoon Kang; Korean J Pathol. 2012;46(1):1-9. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.1

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Abstract PDF

Gastric cancers arise through a multistep process characterized by the progressive accumulation of molecular alterations in which genetic and epigenetic mechanisms have been implicated. Gastric cancer is one of the human malignancies in which aberrant promoter CpG island hypermethylation is frequently found. Helicobacter pylori and Epstein-Barr virus, which are known carcinogens for gastric cancer, are closely associated with enhanced hypermethylation of CpG island loci in gastric non-neoplastic epithelial cells and cancer cells, respectively. Aberrant CpG island hypermethylation occurs early in the multistep cascade of gastric carcinogenesis and tends to increase with the step-wise progression of the lesion. Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of promoter CpG island hypermethylation. In this review, a variety of information is summarized regarding CpG island hypermethylation in gastric cancer.

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Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer
Kie Kyon Huang, Kalpana Ramnarayanan, Feng Zhu, Supriya Srivastava, Chang Xu, Angie Lay Keng Tan, Minghui Lee, Suting Tay, Kakoli Das, Manjie Xing, Aliya Fatehullah, Syed Muhammad Fahmy Alkaff, Tony Kiat Hon Lim, Jonathan Lee, Khek Yu Ho, Steven George Ro
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Journal of Interferon & Cytokine Research.2018; 38(11): 480. CrossRef
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Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NFκB pathway in gastric cancer development
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Case Report

Exuberant Smooth Muscle Cells in Fibroadenoma of the Breast: A Case Report.: Ga Eon Kim, Young Kim, Eun Hui Jeong, Jo Heon Kim, Min Ho Park, Ji Shin Lee; Korean J Pathol. 2010;44(4):431-434.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.431

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Abstract PDF

Smooth muscle cell metaplasia is an extremely rare form of stromal differentiation in fibroadenomas. We describe a case of fibroadenoma with exuberant smooth muscle cells in a 72-year-old woman. The mass was located in the upper central portion of the left breast. It was well circumscribed and its greatest dimension was 3 cm. Histologically, the glandular elements resembled the appearance of fibroadenoma, but the stromal elements were composed of spindle cell bundles with abundant eosinophilic cytoplasm and elongated cigar-shaped nuclei. Neither mitotic activity nor cellular atypia was seen. The stromal cells were immunohistochemically positive for smooth muscle actin, calponin, desmin, and estrogen receptor-beta, but negative for CD34, S-100 protein, p63, CD10, estrogen receptor-alpha, progesterone receptor and cytokeratin. These results proved that the stromal cells showed features of smooth muscle cells.

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Case Reports in Veterinary Medicine.2021; 2021: 1. CrossRef

Original Articles

Squamous Metaplasia of the Pleura.: Hyun Ju Kim, Jeong Hee Lee, Gyung Hyuck Ko; Korean J Pathol. 1995;29(6):792-793.

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Abstract PDF: We report a case of squamous metaplasia of the pleura observed in a 51 year old man. Squamous metaplasia of serosal surface, and in particular of the pleura, is uncommon. The pathogenesis of squamous metaplasia is obscure, but it may be associated with chronic irritation.

Helicobacter pylori Infection and Histopathological Features of Gastric Mucosa.: Gyung Hyuck Ko, Cheol Keun Park, Chun Sik Choi, Heung Bae Park, Jeong Hee Lee, Hye Jung Lee, Hyun Ju Kim, Kwang Ho Rhee; Korean J Pathol. 1996;30(3):199-209.

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Abstract PDF: A microscopic examination of 1,000 cases of gastroscopic biopsy specimens revealed that the prevalence and severity of chronic gastritis, neutrophilic infiltration, and Helicobacter pylori infection increased with advancing age until the age reached about 40, but they decreased thereafter in accordance with the increasing prevalence of intestinal metaplasia. The prevalence and severity of Helicobacter pylori infection, chronic gastritis, and neutrophilic infiltration were proportionately related to each other and to gastric peptic ulcer, but inversely related with intestinal metaplasia and gastric carcinoma. The results suggested that chronic gastritis and gastric peptic ulcer may be associated with Helicobacter pylori infection and that if these lesions persist, intestinal metaplasia may develop with decreased severity of chronic gastritis and Helicobacter pylori infection but, instead, increase of the risk of gastric carcinoma. And it is thought that the cause of the high incidence of gastric carcinoma in Korea may be related to the fact that chronic gastritis and Helicobacter pylori infection develop earlier in life and therefore the prevalence of intestinal metaplasia is higher in Korea than in other countries.

Endometrial Ossification: Clinical and pathological analysis of 7 cases.: Kyu Rae Kim, Dong Hee Choi; Korean J Pathol. 1996;30(3):238-244.

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Abstract PDF: Endometrial ossifications in seven patients who presented with secondary or primary infertility were described. Herein, we described step-by-step bone forming process in the endometrium and we compared the clinicopathological features of metaplastic ossification and fetal remnants. In five of seven patients, metaplasia was unquestionable etiology of ossification, which was ocquired in the healing process of postabortion endometritis. Ossifications were recurred during the follow-up periods after total hysteroscopic removal in 2 cases. Three cases were followed by normal pregnancy, after total hysteroscopic removal of bony spicules in 2 cases and with retaining of bony spicules in 1 case. In one other case, bony spicules of fetal remnants were verified by multiple fetal hair shafts and endochondral bone formation. Therefore, the cause of endometrial ossification can only be determined by histological findings and careful past obstetric history.

Effects of Progesterone Treatment on the Squamous or Morular Metaplasia Associated with Endometrial Hyperplasia.: Kyu Rae Kim, Hee Jeong Ahn; Korean J Pathol. 1996;30(8):680-686.

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Abstract PDF: During evaluation of follow-up curettage of endometrial hyperplasia after progesterone treatment, we have noticed that the foci of squamous or morular metaplasia are persistent or even markedly increased after the hyperplastic glands have all disappeared. These observations have led us to study the histological changes of squamous or morular metaplasia in the hyperplastic endometrium after progesterone treatment and to examine the changes of estrogen receptors(ER) and progesterone receptors(PR) to find out, if there is any pathogenetic role of progesterone administration on the squamous or morular metaplasia. Squamous or morular metaplasia was associated in 21 cases (13.5 %) out of 156 endometrial hyperplasia during the study periods and all of them were associated with complex hyperplasia, but not associated with simple hyperplasia. At follow-up curettage after progesterone treatment, squamous metaplasia newly appeared in 3 cases(20 %), markedly increased in 4 cases(26.7%), persisted in 4 cases(26.7%) and decreased in 4 cases(26.7%), even after hyperplastic glands have all disappeared or were markedly decreased. On immunohistochemical staining, metaplastic foci showed ER- and PR- in 13 cases (87 %) in contrast to the surrounding endometrium and the remaining 2 cases showed minimal ER+ and PR+ confined to several nuclei. Intensity or staining pattern of ER and PR in metaplastic foci were not changed with progesterone treatment. In the background endometrium, intensity of glandular ER+ and PR + was higher than that of the stroma at the initial curettage, however, progesterone treatment predominantly down-regulated glandular ER+ more than stromal ER+. Increment or persistence of squamous metaplasia along the progesterone treatment seemingly would implicate hormonal influences as playing a significant role in the formation of squamous or morular metaplasia and the absence of cellular receptors for these hormones in the metaplastic foci may suggest qualitative changes in the receptors.

Case Report

Eccrine Squamous Syringometaplasia.: Gyeong Sin Park, Lee So Maeng, Chang Seok Kang, Seok Jin Kang, Byung Kee Kim; Korean J Pathol. 1997;31(5):489-491.

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Abstract PDF: An eccrine squamous syringometaplasia (ESS) is defined as a mature squamous metaplasia of the eccrine ducts. The clinical and pathological features of an ESS are presented. Syringometaplasia is a rare lesion, mostly occuring in the extremities, and as far as we know, no report on the ESS has been published in Korean literature. We experienced a case of an ESS occured in a 15 year-old male, who had a tender erythematous plaque in the right knee. The histologic examination revealed some scattered nests of metaplastic squamous epithelium in the deep dermis, associated with acute nonspecific panniculitis. The importance of the ESS is that it histologically simulates the well differentiated squamous cell carcinoma. The histopathologic findings were discussed and a brief review of the literature was made.

Original Articles

Hyperplasia, Metaplasia, and Dysplasia of the Gallbladder Correlation to Gallbladder Adenocarcinoma.: Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(6):527-537.

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Abstract PDF: The correlation of metaplasia to dysplasia and carcinoma in the gallbladder has attracted the attention of many investigators. We mapped and examined a total of 263 cholecystectomized gallbladders to analyze the mucosal changes in the carcinogenesis of the gallbladder. Stones were present in 59.7%, hyperplasia in 28.5%, metaplasia in 55.5% (gastric 37.6%, intestinal 17.9%), dysplasia in 17.1% (low grade 9.1%, high grade 8%) and carcinoma in 7.6%. Metaplasia was more frequently identified in the stone-positive group (62.4%) than in the stone-negative group (45.3%) (P<0.05). Especially, the incidence of intestinal metaplasia was significantly higher in the stone-positive group. Dysplasia and carcinoma were more frequent in the metaplasia-positive group (dysplasia 26.7%, carcinoma 11%) than in the metaplasia-negative group (dysplasia 5.1%, carcinoma 3.4%) (P<0.05). Their incidences were significantly higher in the intestinal metaplasia than in the gastric metaplasia. Forty four percent of the dysplasia-positive cases were associated with carcinoma in the adjacent mucosa but carcinoma was absent in the dysplasia-negative cases. Hyperplasia did not reveal any significant correlation with metaplasia, dysplasia and carcinoma. These results suggest that gallstone is causally related to the metaplasia in the gallbladder and the metaplasia-dysplasia- carcinoma sequence exists in the gallbladder.

Expression of H-ras, erb B2, and p53 Proteins in Gastric Intestinal Metaplasia Associated with Cellular Atypism.: Han Ik Bae, Dong Hoon Kim, Jung Ran Kim; Korean J Pathol. 1997;31(9):862-872.

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Abstract PDF: Intestinal metaplasia (IM) have long been thought to play a role in the pathogenesis of gastric intestinal adenocarcinoma, but not in that of diffuse cancer. We studied 20 normal gastric mucosa, 90 IM, 39 atypia (dysplasia or adenoma), and 51 adenocarcinoma to evaluate the expression of p53, erb B2, and H-ras p21 proteins and to assess the correlation with IM (esp. type III IM, revealing positive HID-AB/PAS for sulfomucin). Positive rate of HID-AB staining revealed an increased trend in comparison between IM, atypia and adenocarcinoma. It was the highest in mucinous carcinoma, but it was not correlated with positive oncoprotein expressions. Positive rates of oncoproteins revealed increased trends in comparison between IM, dysplasia or adenoma and adenocarcinoma in c-erb B2 and p53 (P<0.01). The positive rates were highest in intestinal adenocarcinoma (50.0% and 54.2%, respectively). Rates were lowest in biopsy tissue of IM (4.4% and 8.7%, respectively). The expression of H-ras p21 was not significant in gastric carcinogenesis. There was no significant correlation between oncoproteins and other clinical parameters, such as depth of invasion, differentiation, size and nodal metastasis of the tumors. Therefore, we suggest that p53 and erb B2 may play a role in the carcinogenesis of gastric intestinal adenocarcinoma.

Correlation of the Intestinal Metaplasia Subtypes and Gastric Carcinoma.: Hwa Eun Oh, Mee Ja Park, Jong Sang Choi; Korean J Pathol. 1997;31(12):1272-1281.

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Abstract PDF: Helicobacter pylori, loss of basement membrane, atrophy, type III intestinal metaplasia, adenomatous polyposis coli (APC) gene mutations and altered p53 function were believed as a factor to develop the gastric adenocarcinomas. To investigate the incidence and prevalence of Helicobacter pylori, intestinal metaplasia and atrophy, 120 gastrectomy specimens collected from patients with gastric adenocarcinoma (100 cases) and non-neoplastic conditions (20 cases) were studied. Intestinal metaplasia can be classified as type I (complete), type II (incomplete, sulfomucin-negative) and type III (incomplete, sulfomucin-positive) by Filipe and Jass. The incidence of intestinal metaplasia of gastric adenocarcinoma was 96% compared with the incidence of 75% in non-neoplastic conditions. The type I and type II were more common than type III and were present in both non-neoplastic conditions (75%) and adenocarcinoma (74%). In contrast, type III intestinal metaplasia was seen in only 20% of intestinal metaplasia-positive cases, all of which (22 of 22) were from patients with adenocarcinoma. The high specificity of type III intestinal metaplasia might be acceptable for screening purposes, but its sensitivity of 22% for gastric adenocarcinoma is low. Helicobacter pylori were detected in 96% of adenocarcinoma cases and 100% of non-neoplastic cases. Atrophy was detected in 50% of non-neoplastic cases and in 57% of adenocarcinoma cases. The data thus confirms a significant relation between incomplete sulfomucin-secreting intestinal metaplasia (type III) and gastric carcinoma, especially intestinal type (p<0.01). Thus, the type III intestinal metaplasia should be considered a risk factor and its presence in a biopsy specimen should prompt close surveillance.

Carcinosarcoma of the Female Genital Tract: Immunohistochemical study on transitional area further supports the metaplastic origin.: Chan Pil Park, Joo Seob Keum, Gu Kong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(5):370-377.

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Abstract: Carcinosarcoma of the female genital tract, also called malignant mixed mullerian tumor (MMMT), is a rare and relatively aggressive tumor with various homologous and heterologous components. There have been various studies to find prognostic factors and to investigate the histogenesis, including tissue culture, electron microscopy, and immunohistochemical studies. We investigated carcinomatous, sarcomatous, and transitional areas of 6 cases of carcinosarcoma of the uterus and ovary by using epithelial and mesenchymal markers. Immunohistochemical profiles of the transitional areas were significantly different from those of carcinomatous and sarcomatous areas. Immunoreactivities for cytokeratin and epithelial membrane antigen (50% and 22.2%) were weaker than those of carcinomatous areas (95.2% and 100%), but stronger than those of sarcomatous areas (11.1% and 5.6%)(p<0.01). In transitional areas, vimentin, smooth muscle actin and S-100 protein were more strongly expressed than in carcinomatous areas, but more weakly expressed than in sarcomatous areas (p<0.01, p<0.01, and p=0.018, respectively). Myoglobin was entirely negative in carcinomatous areas and immunoreactive in minor portions of transitional and sarcomatous areas (22.2% and 16.7%, respectively). These results suggest that the transitional areas are between the carcinomatous and sarcomatous nature in differentiation, further supporting that the carcinosarcomas of the female genital tract may arise, through metaplastic change, from a type of carcinoma.

Cytologic Features of Papillary Immature Metaplasia of Uterine Cervix.: Hye Sun Kim, Mee Im Seon, Yee Jung Kim, Hy Sook Kim; J Pathol Transl Med. 2002;13(1):21-27.

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Abstract PDF: Papillary immature metaplasia (PIM) of the uterine cervix (immature condyloma) is a subset of low grade squamous intraepithelial lesion (LSIL) which is frequently associated with human papilloma virus (HPV) types 6 and 11. The histologic features of PIM include filiform papillae lined by evenly spaced immature metaplastic-type cells with frequent nucleoli, mild anisokaryosis, and a low mitotic index. To characterize the cytologic changes associated with PIM, we analyzed 14 cases of PIM from our file. We reviewed biopsy slides and the cervicovaginal smears taken proximate to the time of biopsy. Histologically, nine cases had either flat condyloma (7 cases) or high grade squamous intraepithelial lesion (HSIL) (2 cases). Cytologic changes included cells in various stages of maturation with karyomegaly (14 cases), cells with irregularities in the nuclear membrane (13 cases), intermediate cells with karyomegaly(13 cases), cells with binucleation (13 cases), and aborted koilocytes (11 cases). Cervicovaginal smears from all cases were interpreted as atypical squamous cells of undetermined significance (ASCUS), NOS or ASCUS, rule out squamous intraepithelial lesion (SIL) or LSIL in two cases with flat condyloma or HSIL in a case with severe dysplasia. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings, but cytologic findings may resemble variable reactive conditions and immature HSIL. Therefore, it is difficult to diagnose PIM by cytology alone. However, the meticulous efforts for making the cytologic diagnoses which can induce active management of patients are recommended because PIM is a variant of LSIL and frequently has a flat condyloma or HSIL.

Case Reports

Fine Needle Aspiration Cytology of Chronic Sclerosing Sialadenitis with Mucinous Metaplasia in Parotid Gland: A Case Report.: Jae Yeon Seok, Woo Hee Jung, Xu Xiang Fan, Jin Kim, Soon Won Hong; J Pathol Transl Med. 2005;16(2):102-105.

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Abstract PDF: Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a benign chronic inflammatory lesion of the salivary gland. Here, we describe a case of chronic sclerosing sialadenitis with mucinous ductal metaplasia in a parotid gland, which was confused with low-grade mucoepidermoid carcinoma on aspiration cytology.

Fine Needle Aspiration Cytology of the Warthin's Tumor Misinterpretated as Squamous Cell Carcinoma: A Case Report.: Kyungji Lee, Chan Kwon Jung, Ahwon Lee, Kyo Young Lee, Chang Suk Kang; J Pathol Transl Med. 2005;16(2):106-109.

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Abstract PDF: We report a case of Warthin's tumor of the parotid gland in a 53?year?old man, which is incorrectly diagnosed as squamous cell carcinoma. Fine needle aspiration cytology(FNAC) smear obtained from the right parotid gland revealed scattered epithelial cell clusters or nests in a diffuse inflammatory and necrotic background. Some epithelial cells had squamoid appearance showing variable sized bizarre shaped nuclei. They had abundant of dense eosinophilic keratinized cytoplasm. Occasionally, parakeratotic cells were also present. These cytologic findings with significant atypia and necrotic background made diagnosis as squamous cell carcinoma. But, the resection specimen from this patient showed classic Warthin's tumor in addition to abundant areas of inflammation and squamous metaplasia. Metaplastic or infarcted Warthin's tumor in the salivary gland may be confused with false positive diagnosis of malignancy on FNAC. Therefore, cytopathologist should have adequate awareness of potential of erroneous diagnosis in FNAC of Warthin's tumor.

Minimal Deviation Endometrioid Adenocarcinoma of the Uterine Cervix: A Case Report.: Kye Won Kwon, Susie Chin, Hee Kyung Kim, Eun Seok Koh, Kyu Rae Kim, Kye Hyun Nam; Korean J Pathol. 2008;42(4):240-243.

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Abstract PDF: We describe here a case of minimal deviation endometrioid adenocarcinoma (MDEA) of the uterine cervix that was initially suspected according to the abnormal cytologic findings in a 39-year-old woman. The Papanicolaou (pap) smear showed many neoplastic glandular cells in monolayered sheets, rosettes, and clusters with palisading and feathering borders. The tumor cells had oval, hyperchromatic nuclei, with chromatin clumping and small nucleoli. Histologic examination disclosed endometrial-type glands with a bland, isolated, mainly rounded appearance and these glands were widely scattered deep into the cervical stroma with only scant stromal reaction. An association of MDEA with tubo-endometrioid metaplasia or cervical endometriosis has been suggested by identifying the tubo-endometrioid glands in the vicinity of the MDEA.

Original Article

Relationship of Gastric Metaplasia of the Duodenum with Age, Duodenal Ulcer and Helicobacter pylori Infection.: Dae Hyun Song, Dong Chul Kim, Jong Sil Lee, Jeong Hee Lee, Hyun Jin Kim, Hee Shang Youn, Gyung Hyuck Ko; Korean J Pathol. 2007;41(4):217-223.

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Abstract PDF: BACKGROUND
Gastric metaplasia of the duodenum is thought to be associated with the pathogenesis of duodenal ulcer. We investigated the pathological features of gastric metaplasia and their relation to age, gender, duodenal ulcer and H. pylori infection.
METHODS
We reviewed the duodenal endoscopic findings of 535 patients (age range: 0 to 87) and the microscopic slides of the duodenal biopsy specimens.
RESULTS
Gastric metaplasia was first noted at the age of 4 and the prevalence increased thereafter until the patients' mean age reached about 30. The prevalence of gastric metaplasia was 53.7% after 30 years of age. As the metaplasia became severer, it became more polypoid in appearance and it more often contained parietal cells. Gastric metaplasia was more frequently observed or severe in duodenal ulcer patients, in males and in the first portion of the duodenum than in patients without duodenal ulcer, in females and in the second portion, respectively. There was a lack of correlation between gastric metaplasia and H. pylori infection.
CONCLUSIONS
The prevalence and/or severity of gastric metaplasia of the duodenum increases with age, and it is thought that most duodenal ulcers develop in the areas of gastric metaplasia.

Case Reports

Endometrial Mucinous Adenocarcinoma with Extensive Squamous Differentiation: A Case Report.: Ho chang Lee, Pil Gyu Hwang, Soo Youn Cho, Young S Park, In Ae Park; Korean J Pathol. 2003;37(6):438-441.

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Abstract PDF: Endometrial mucinous adenocarcinoma occurs in 1-9% of endometrial adenocarcinomas and adenocarcinoma with squamous differentiation in approximately 25%. We report a rare case of mucinous adenocarcinoma with squamous differentiation in a 53-year-old woman. Curetting biopsies of the endometrial lesion were taken twice after hormone replacement therapy, which lasted for four months. Because the squamous differentiation was so extensive, the initial diagnosis based on each curetting specimen was squamous papilloma. A total hysterectomy was performed and the tumor was revealed to be a mucinous adenocarcinoma with squamous differentiation. We subsequently discussed the pathogenesis and prognosis of this type of tumor.

Pulmonary Alveolar Proteinosis accompanied by Osseous Metaplasia: A case report.: Ae Ree Kim, Hyun I Cho, Han Kyeom Kim, Jong Sang Choi, In Sun Kim; Korean J Pathol. 1994;28(5):547-549.

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Abstract PDF: The authors experienced a case of pulmonary alveolar proteinosis. A 58-year-old woman presented with 6 months duration of cough sputum and multiple patch mottled densities in both lung fields. Major histologic finding was filling of the alveoli by Periodic-Acid-Schiff-positive proteinaceous material with maintenance of normal alveolar architecture. Osseous metaplasia was seen in the alveolar space, focally. Ultrastructural study revealed numerous lamellar bodies in alveolar spaces. The immunohistochemical study using antibody to surfactant apoprotein revealed positive reaction in proteinaceous material.

Squamous Metaplasia in Tubular Adenoma of Sigmoid Colon: A case report.: Soo Min Kang, Weon Seo Park, Woo Ho Kim, Yong Il Kim; Korean J Pathol. 1993;27(6):663-665.

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Abstract PDF: The occurrence of squamous metaplasia(morule) in colorectal mucosa and adenocarcinoma, althrough rare, has been well documented. In contrast, very little mention has been given to mature squamous cells seen in colorectal polyps or adenomas. A 42-year-old woman presented with a 2-month history of diarrhea and melena. Proctosigmoidoscopy revealed a 4 cm-sized polypoid tumor 20 cm above the anal verge. Colonoscopic biopsy showed tubular adenoma, and a segmental resection of sigmoid colon was done. Microscopically, the tumor was c classical tubular adenoma containing multiple solid nests of squamous cells scattered only in the neoplasm; the squamous nests were generally small, and some showed direct continuity with adenomatous glands. The squamous cells were keratinizing and had regular nuclei with no mitotic activity. The importance of this phenomenon lies in its pathologic recognition, and the findings suggest that awareness of this rare occurrence in colorectal polyps should avert such overdiagnosis, and consequently prevents unnecessary radical surgery.

Original Articles

An Image Analytical Study on the Structural Spectrum of Intestinal Metaplasia-Dysplasia-Carcinoma of the Stomach.: Sang Woo Juhng, Dong Ha Park, Ji Shin Lee, Kyu Hyuk Cho; Korean J Pathol. 1993;27(1):50-57.

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Abstract PDF: Intestinal metaplasia and dysplasia of the stomach have been stressed as precursors of gastric carcinoma of the intestinal type, although their preneoplastic nature is still debated. In this study, the cytomorphometric and cytokinetic spectra of the suggested preneoplastic and neoplastic lesions of the stomach were investigated. From the resected stomachs of early gastric carcinoma of intestinal type, areas of normal, intestinal metaplasia, dysplasia, and carcinoma were selected. They were immunostained for proliferating cell nuclear antigen, counterstained with propidium iodide, and various nuclear parameters were measured by image analysis. Normal and intestinal metaplastic mucosae differed by the localization of proliferation zone, but not by nuclear profile area, circular shape factor, and proliferation index. In dysplasia, proliferation zone covered large parts of the dysplastic area. Nuclear profile area and proliferation index were larger whereas circular shape factor was smaller than in normal or intestinal metaplasia. Carcinomatous lesion had diffuse proliferation activity, the largest nuclear profile area and proliferating index, and circular shape factor in-between those of normal or intestinal metaplasia and dysplasia. The above results showed a structural spectrum among normal of intestinal metaplasia, dysplasia, and carcinoma of intestinal type in cytomorphometric and cytokinetic terms. The structural spectrum raises the possibility that dysplasia of the stomach is a preneoplastic lesion.

Gastric Metaplasia in Duodenum.: Young Lyun Oh, Mi Kyung Kim, Woo Ho Kim, Yong Il Kim; Korean J Pathol. 1992;26(3):242-246.

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Abstract PDF: The partial replacement of the human duodenal mucosa by epithelial cells containing gastric-type mucus(gastric metaplasia) is not an uncommon finding, and an emphasis on its etiological role in duodenal ulcerogenesis has been proposed. It is unclear, Furthermore, all the previous studies were done with endoscopic biopsy specimens. We reviewed a total of 118 surgically resected stomachs with attached duodenal stumps(24 cases of gastric ulcer, 15 duodenal ulcer and 79 advanced gastric cancer). The gastric-type mucous cells were homogeneously stained red with PAS in contrast to the intestinal cells which gave a strong PAS stainability only along the the brush border. The gastric metaplasia was seen near the tips or on the sides of the villi and occasionally in the crypts. It was observed in 8 cases(53%) in duodenal ulcer, 12 cases(50%) in gastric ulcer and 29 cases(37%) in gastric cancer. There were no significant statistical differences in incidence among the groups. Nevertheless, diffuse form of gastric metaplasia was more prevalent in patients with duodenal ulcer(p<0.05).

Case Report

Keratinizing Desquamative Squamous Metaplasia of the Upper Urinary Tract: A case report.: Soo Min Kang, Sun Young Kim; Korean J Pathol. 1991;25(1):76-80.

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Abstract PDF: Keratinizing desquamative squamous metaplasia of the transitional epithelium occurs rarely in the upper urinary tract, especially in the ureter. It is associated in most cases with long-standing chronic inflammation but the exact pathogenesis is unknown, and the relationship to cancer has continued to be controversial. More cases should be accumulated for a better assessmnt of this lesion. Recently, we experienced a case of keratinizing desquamative squamous metaplasia in the renal pelvis, adjacent calyces and ureter following acute and chronic pyelonephritis. Herein, we are presenting our case with a review of literatures.

Original Article

Clinicopathologic Study of the Endometrium of Dysfunctional Uterine Bleeding.: Nam Hoon Cho, Chan Il Park, In Joon Choi; Korean J Pathol. 1989;23(1):65-74.

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Abstract PDF: One of the most common symptoms in gynecologic disorders is an abnormal utirine bleeding, of which dysfuncyional uterine bleeding (DUB) is frequently encountered. DUB is defined as an endocrinologic imbalance of the axis of hypothalamus-pituitary-ovary-endometrium without organic diseases such as a neoplasm, and inflammation, a pregnancy, a trauma, Although the correct diagnosis of DUB depends on various assessements such as a menstrual cycle, basal body temperature, endocrine assay, vaginal cytology and endometrial histology, in many circumstances pathologist have only the endometrial histology with trivial clinical information to make a diagnosis. Therefore, the present study was aimed at assessing the pattern of the endometrium as precisely as possible. The histologic pattern was classified according to the Handrickson and kempson classification (1980). The authors also attempted to correlate the non-neoplastic metaplasia with the endometrial histology. The material consisted of 447 cases of endometrial curettage specimens diagnosed clinically as DUB during recent 4 years. The histologic examination was carried out through the routine formalin fixed-paraffin embedding method, followed by hematoxylin-eosin staining in routine and other special staining as required. The following results were obtained; 1) The pattern of the endometrium in DUB was predominently the proliferative type (239 cases, 65.55%). Of these 293 cases, 144 were of the abnormal proliferatrive phase, and particulary most were the disordered proliferative phase. The remaining 154 cases (34.45%) were found to have secretory endometrium, of which 50 cases belonged to the abnormal secretory type. Most of the cases shewing abnormal secretory patterns appeared dyssynchronous or underdeveloped. 2) Of the 361 patients with DUB for whom the clinical records were available, 197 (54.57%) were non-ovulatory and 118 (32.69%) were ovulatory. 3) Non-neoplasic metaplasia was found in 87 cases, of which ciliiated and papillary types were most common. The endometrium was of the proliferative phase in 73.56% of the cases with metaplasia, and the disordered proliferative pattern showed a particular correlation with the metaplasia (44 cases). 4) Among 63 postmenopausal DUB patients, 52 (82.53%) appeared to have the proliferative endometrium, and in particular 23 (36.51%) had the disordered proliferative endometrium.

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