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Volume 46(3); June 2012
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Original Articles
Clinicopathological Analysis of 21 Thymic Neuroendocrine Tumors
Soomin Ahn, Jae Jun Lee, Sang Yun Ha, Chang Ohk Sung, Jhingook Kim, Joungho Han
Korean J Pathol. 2012;46(3):221-225.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.221
  • 7,367 View
  • 70 Download
  • 24 Citations
AbstractAbstract PDF
Background

Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia.

Methods

We reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features.

Results

It showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver.

Conclusions

In conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II)
Jin Hee Sohn, Gyungyub Gong, Kyu Rae Kim, Chang Suk Kang, Youn Soo Lee, Jin Man Kim, Woo Hee Jung, Kwang Sun Suh
Korean J Pathol. 2012;46(3):226-232.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.226
  • 7,793 View
  • 46 Download
  • 2 Citations
AbstractAbstract PDF
Background

Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts.

Methods

As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP.

Results

Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature.

Conclusions

Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

Urinary Decoy Cell Grading and Its Clinical Implications
Myoung Ju Koh, Beom Jin Lim, Songmi Noh, Yon Hee Kim, Hyeon Joo Jeong
Korean J Pathol. 2012;46(3):233-236.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.233
  • 6,548 View
  • 38 Download
  • 4 Citations
AbstractAbstract PDF
Background

Examination of urine for decoy cells (DCs) is a useful screening test for polyomavirus (PV) activation. We explored the significance of the amount of DCs in persistent shedding, PV nephropathy and acute rejection.

Methods

A case-controlled study was performed in 88 renal allograft patients who had DCs detected at least once in four or more urine samples.

Results

Fifty one patients were classified into the high-grade shedding group (HG) and 37 patients into the low-grade shedding group (LG) according to DC shedding (≥10 or <10 DCs/10 high power field [HPF]). DC shedding of more than three consecutive months was significantly more prevalent in the HG as compared with their LG counterparts (p<0.0001). Urinary DCs were present for more than one year in 29.4% of the HG and 8.1% of the LG. Real-time polymerase chain reaction for PV was higher in both urine (51.4% vs. 11.1%) and plasma (9.1% vs. 0%) of the HG than the LG. The prevalence of PV nephropathy was higher in the HG than the LG (p=0.019). However, there was no significant difference in the prevalence of acute rejection.

Conclusions

Shedding of ≥10 DCs/10 HPF is associated with sustained shedding, polymerase chain reaction positivity and PV nephropathy, but not a predictor of acute rejection.

Cyclooxygenase-2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma
Ji Won Lee, Jeong Hwan Park, Ja Hee Suh, Kyung Han Nam, Ji-Young Choe, Hae Yoen Jung, Ji Yoen Chae, Kyung Chul Moon
Korean J Pathol. 2012;46(3):237-245.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.237
  • 6,496 View
  • 30 Download
  • 13 Citations
AbstractAbstract PDF
Background

The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines.

Methods

Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines.

Results

Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity.

Conclusions

This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas
Hyoun Wook Lee, Ki Hoon Song, Jin Woo Hong, Su Young Jeon, Dong Yeob Ko, Ki Ho Kim, Hyuk Chan Kwon, Suee Lee, Sung Hyun Kim, Dae Cheol Kim
Korean J Pathol. 2012;46(3):246-252.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.246
  • 6,380 View
  • 37 Download
  • 10 Citations
AbstractAbstract PDF
Background

This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters.

Methods

We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors.

Results

The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005).

Conclusions

Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

The Utility of p16INK4a and Ki-67 as a Conjunctive Tool in Uterine Cervical Lesions
Sangho Lee, Hyunchul Kim, Hyesun Kim, Chulhwan Kim, Insun Kim
Korean J Pathol. 2012;46(3):253-260.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.253
  • 7,723 View
  • 72 Download
  • 5 Citations
AbstractAbstract PDF
Background

Immunohistochemical staining for p16INK4a and Ki-67 has been used to improve the accuracy in making a diagnosis of the uterine cervix cancer on biopsy. This study was conducted to examine the usefulness of these markers in the pathological diagnosis based on cervical biopsy.

Methods

We selected a consecutive series of 111 colposcopically directed cervical punch biopsies. Using these biopsy samples, we performed an immunohistochemical staining for p16INK4a and Ki-67 to establish a diagnosis. The slides were circulated among four pathologists in a sequential order: the hematoxylin and eosin (H&E) slide, H&E slide and p16INK4a-stained slide, and H&E slide, p16INK4a- and Ki-67-stained slides.

Results

The overall rates of the concordance in the first, the second, and the third diagnoses were 77.5%, 82.0%, and 82.0%, respectively. The rate of the concordance in the diagnosis of cervical intraepithelial neoplasm (CIN) 2/3 was increased from 62.2% to 73.0%. But there was a variability in the rate of the revision of the diagnosis between the pathologists. With the application of criteria for interpreting the expressions of p16INK4a and Ki-67, benign and CIN 1 lesions showed a p16INK4a expression score of 0 or 1. But CIN 2 and CIN 3 lesions showed a p16INK4a expression score of 2 and 3, respectively.

Conclusions

The immunostain for p16INK4a and Ki-67 might be useful in reducing an inter-observer variability. But criteria for interpreting both markers should be strictly applied.

The Expression of Pigment Epithelium-Derived Factor in Bladder Transitional Cell Carcinoma
Tae Jung Jang, Sung Woo Kim, Kyung Seop Lee
Korean J Pathol. 2012;46(3):261-265.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.261
  • 4,905 View
  • 20 Download
  • 3 Citations
AbstractAbstract PDF
Background

Pigment epithelium-derived factor (PEDF) is an anti-angiogenic factor. The purpose of this study is to examine the involvement of PEDF in the angiogenesis and biological behavior of bladder transitional cell carcinoma (TCC).

Methods

We examined the expression of PEDF in 99 bladder TCCs and ten non-neoplastic tissues, and evaluated microvessel density (MVD).

Results

The positive immunoreactivity for PEDF was seen in normal urothelium in 60% (6/10) and TCC in 13% (13/99). The PEDF expression had a significant correlation with MVD, i.e., a low MVD in 42% (5/12), a middle MVD in 11% (8/76) and a high MVD 0% (0/11) of tumors. The PEDF expression was not significantly correlated with the differentiation and invasion of TCC, but the degree of MVD was significantly higher in both high grade TCC and the pT2 tumors.

Conclusions

The degree of PEDF expression is significantly higher in normal bladder urothelium than bladder TCC; it is inversely correlated with the angiogenesis; and it is not related to the differentiation and progression of TCC. It can therefore be concluded that bladder TCC would initially occur if there is a lack of the PEDF expression.

Metastatic Carcinomas to the Oral Cavity and Oropharynx
Su-Jin Shin, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Sung Bae Kim, Sang-wook Lee, Kyung-Ja Cho
Korean J Pathol. 2012;46(3):266-271.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.266
  • 7,019 View
  • 49 Download
  • 16 Citations
AbstractAbstract PDF
Background

Metastases to the oral/oropharynx are very rare and their diagnosis is challenging.

Methods

We reviewed pathologic data for malignant tumors of the oral/oropharynx that were diagnosed at the Asan Medical Center, Seoul, Korea from 1995 until 2010.

Results

Twenty-nine cases of oral/oropharyngeal metastases were retrieved, comprising 2.0% of 1,445 malignancies. The most common primary sites were the liver and lung, followed by the stomach, colon, breast, prostate, and kidney. The gingiva was the most common metastatic site, followed by the tonsil/pillar, mandible, tongue, tongue base, palate mucosa, mouth floor, and buccal mucosa. Intervals between detection of primary tumors and metastases were variable, from -1 month to 104 months. Ten patients with lung (7 cases), liver, stomach, and kidney carcinomas manifested with oral/oropharyngeal metastases as the first sign of systemic metastases. The majority of patients had died within one year of the onset of an oral/oropharyngeal metastasis, but exceptionally long-lived cases were also present. The survival periods of patients with lung cancers were longer than those of patients with non-pulmonary tumors.

Conclusions

An awareness of the incidence, common primary sites, metastatic subsites, and metastatic courses or patterns of oral/oropharyngeal metastases is helpful in the diagnosis of metastatic carcinomas.

Case Reports
Tumor Budding and Recurrence in Submucosal Invasive Colorectal Cancers of Favorable Histology: Case Reports of Two Early Colorectal Cancers with Advanced Recurrences
Heae Surng Park, Hee Jin Chang, Ji Won Park, Byung Chang Kim, Dae Kyung Sohn, Chang Won Hong, Ji-Yeon Baek, Sun Young Kim, Hyo Seong Choi, Jae Hwan Oh
Korean J Pathol. 2012;46(3):272-277.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.272
  • 6,461 View
  • 46 Download
  • 3 Citations
AbstractAbstract PDF

Complete resection of submucosal invasive colorectal cancer (SICC) showing favorable histology is regarded as curative. We report on two cases of SICC showing recurrence within 5 years despite complete resection. The first patient was a 68-year-old woman with well differentiated rectal adenocarcinoma invading the superficial submucosa, which recurred after 4.7 years. The second patient was a 53-year-old man with pT1N0 moderately differentiated colonic adenocarcinoma. He developed widespread tumor recurrence after 3.9 years. Retrospective pathologic review of the original tumors showed multiple foci of tumor budding at the invasive front. Immunohistochemical staining for D2-40 of deeper levels of the paraffin blocks showed rare foci of small lymphatic invasion. Tumor budding at the invasive front may be an important indicator for SICC aggressiveness or may reflect early lymphatic invasion. More aggressive pathologic examination and follow-up is required for patients with SICC showing tumor budding, even in the absence of unfavorable histologic findings.

Squamoid Eccrine Ductal Carcinoma of the Scalp
Yong-Han Jung, Hye-Jung Jo, Mi-Seon Kang
Korean J Pathol. 2012;46(3):278-281.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.278
  • 7,382 View
  • 62 Download
  • 9 Citations
AbstractAbstract PDF

Squamoid eccrine ductal carcinoma (SEDC) is an exceedingly rare tumor that shows both squamous and adnexal ductal differentiation. We report a case of this unusual tumor occurring on the occiput of a 53-year-old man. A histopathological examination revealed a nodular lesion infiltrating the dermis and subcutaneous tissue with numerous duct-like structure and squamoid differentiation foci. Five months later, the patient presented with a palpable mass at the site of the previous excision and the right side of the neck. Sono-guided fine needle aspiration of the right neck mass was performed and was diagnosed as a metastastasis of a lymph node. A right neck node dissection and re-excision of the occiput was performed. The histopathological findings were similar, but squamoid differentiation was more prominent than that in the previous lesion. Because of the rarity of SEDC, little is known about its biological behavior and optimal treatment.

Papillary Carcinoma of Thyroid Metastatic to Adenocarcinoma In Situ of Lung: Report of an Unusual Case
Kyoung Min Kim, Yo Na Kim, Hyun Hee Chu, Heung Yong Jin, Min Ho Kim, Myoung Ja Chung
Korean J Pathol. 2012;46(3):282-286.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.282
  • 5,691 View
  • 33 Download
  • 6 Citations
AbstractAbstract PDF

The tumor-to-tumor metastasis is a rare event. The lung tumors are the most common donor tumors in tumor-to-tumor metastasis, but are exceedingly rare as a recipient. Here, we report a case of papillary thyroid carcinoma (PTC) metastasizing to adenocarcinoma in situ (AIS, formerly bronchioloalveolar carcinoma) of the lung in a 44-year-old woman who underwent total thyroidectomy for PTC 8 years ago. To the best of our knowledge, the present case is the first case reporting on PTC metastasized to AIS. A review of the relevant literature is presented.

Gastric Adenocarcinoma of Fundic Gland Type: Report of Three Cases
Eun Su Park, Young Eun Kim, Cheol Keun Park, Takashi Yao, Ryoji Kushima, Kyoung-Mee Kim
Korean J Pathol. 2012;46(3):287-291.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.287
  • 8,035 View
  • 83 Download
  • 18 Citations
AbstractAbstract PDF

Recently, fundic gland type gastric adenocarcinoma (GA-FG) has been reported as a new entity. This report describes GA-FG among Koreans for the first time. From March 2008 to July 2010 we identified only three cases of GA-FG out of over 6,000 GAs resected by endoscopy or surgery. Cell differentiation by mucin proteins, pepsinogen-I, and H+/K+-ATPase was evaluated. All three cases were male patients and diagnosed as early stage GA. Histologically, GA-FGs were well-differentiated adenocarcinoma with pale gray-blue, basophilic columnar or cuboidal cells and mildly enlarged nuclei, resembling chief cells. All three cases were positive for pepsinogen-I and were classified as gastric mucin phenotype. Among three histologic subtypes of GA-FG, since tumors were mainly composed of chief cells, our three cases were classified as chief cell predominant type. In conclusion, GA-FG is very rare among Koreans and pepsinogen-I and MUC6 expression are typical immunohistochemical findings in GA-FG suggesting differentiation toward fundic glands.

Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach: Report of Two Cases and Review of the Literature
Youngran Kang, Wonkyung Jung, In-Gu Do, Eui Jin Lee, Min Hyeong Lee, Kyoung-Mee Kim, Jongsang Choi
Korean J Pathol. 2012;46(3):292-296.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.292
  • 6,862 View
  • 51 Download
  • 25 Citations
AbstractAbstract PDF

Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach is a recently recognized entity. Because of its rarity, only 22 cases have been reported in the English-language literature and most of these are single case reports. We report two cases of gastric PAMT. The tumor cells were bland and plexiform arranged in a myxoid stroma, which was positive for alcian blue. Immunohistochemically, the tumor cells were positive for smooth muscle actin, but negative for c-kit, CD34, desmin, S-100 protein, epithelial membrane antigen, neurofilament, and protein kinase C-theta. Mutation analyses for exon 9, 11, 13, and 17 of KIT genes and 12, 14, and 18 of the platelet-derived growth factor receptor alpha (PDGFRA) genes were performed and the tumors were wild-type for mutation.

Osteoclast-like Giant Cell Tumor of Parotid Gland with a Carcinomatous Component: A Case Report
Jung Wook Yang, Hyeon Cheol Kim, Jeong Hee Lee, Jong Sil Lee, Dong Chul Kim, Dae Hyun Song, Jin Pyeong Kim, Gyung Hyuck Ko
Korean J Pathol. 2012;46(3):297-301.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.297
  • 5,909 View
  • 46 Download
  • 5 Citations
AbstractAbstract PDF

The giant cell tumor of the salivary gland is very rare, and 20 cases have been reported in the English-language literature. We report an additional case. A 57-year old man had noticed a mass in the right parotid area for several weeks. The diagnosis using aspiration cytology was a giant cell tumor possibly with a carcinomatous component. Superficial parotidectomy was carried out. The resected parotid gland contained a 1.8 cm-sized well-circumscribed brownish tumor. Histologically the tumor consisted of evenly distributed osteoclast-like giant cells, mononuclear cells and two small foci of a carcinomatous component. The osteoclast-like giant cells and mononuclear cells were positive for vimentin and CD68, and the carcinomatous component was positive for cytokeratin and epithelial membrane antigen. There was no metastatic lesion in the cervical lymph nodes. We believe this is the first case in Korea of an osteoclast-like giant cell tumor of the parotid gland.

Cytologic Findings of Thyroid Carcinoma Showing Thymus-like Differentiation: A Case Report
Sunhee Chang, Mee Joo, Hanseong Kim
Korean J Pathol. 2012;46(3):302-305.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.302
  • 7,110 View
  • 42 Download
  • 11 Citations
AbstractAbstract PDF

Carcinoma showing thymus-like differentiation (CASTLE) is a rare carcinoma of the thyroid or adjacent soft tissue of the neck with a histologic resemblance to thymic epithelial tumors. Although the fine-needle aspiration (FNA) plays a central role in the initial evaluation of thyroid nodules, few reports about the cytologic findings of CASTLE have been found according to a review of literatures. We report cytologic findings of a case of CASTLE. A 34-year-old woman presented with a 2-month history of sore throat. The FNA showed that the smear was composed of three dimensional clusters and sheets. The tumor cells were round to ovoid with high nuclear : cytoplasmic ratios. The nuclei were vesicular with small nucleoli. There were some tumor cells showing keratinization. Some lymphocytes were found on the background and within clusters. The presence of poorly-differentiated tumor cells with a focal keratinization and a lymphocytic background on the FNA is suggestive of CASTLE.


JPTM : Journal of Pathology and Translational Medicine