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Volume 47(2); April 2013
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Review & Perspectives
Acinar Cell Carcinoma of the Pancreas: Clinical and Cytomorphologic Characteristics
Adam D. Toll, Ralph H. Hruban, Syed Z. Ali
Korean J Pathol. 2013;47(2):93-99.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.93
  • 12,697 View
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  • 13 Citations
AbstractAbstract PDF

Acinar cell carcinoma is a rare malignant epithelial neoplasm with predominantly exocrine acinar differentiation and is seen primarily in older men (mean age, 62 years). The presenting symptoms are usually non-specific, and jaundice is often not present. Symptoms relating to the overproduction and release of lipase into the circulation are present in 10-15% of patients. Characteristic cytomorphologic features include a population of cells with minimal pleomorphism, eccentrically placed nuclei with a single prominent nucleoli and moderate hyperchromasia. The cytoplasm is finely granular, and the background may contain granular debris secondary to cytolysis. A significant proportion of the cases also have a minor neuroendocrine component or scattered neuroendocrine cells. Approximately 50% of patients have metastatic disease at presentation, often restricted to the regional lymph nodes and liver. The prognosis is poor, only slightly better than that of pancreatic ductal adenocarcinoma.

Guideline Recommendations for EGFR Mutation Testing in Lung Cancer: Proposal of the Korean Cardiopulmonary Pathology Study Group
Hyo Sup Shim, Jin-Haeng Chung, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Geon Kook Lee, Soon-Hee Jung, Se Jin Jang
Korean J Pathol. 2013;47(2):100-106.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.100
  • 8,094 View
  • 56 Download
  • 9 Citations
AbstractAbstract PDF

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

Original Articles
EGFR Gene Amplification and Protein Expression in Invasive Ductal Carcinoma of the Breast
Won Hwangbo, Jeong Hyeon Lee, Sangjeong Ahn, Seojin Kim, Kyong Hwa Park, Chul Hwan Kim, Insun Kim
Korean J Pathol. 2013;47(2):107-115.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.107
  • 10,065 View
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  • 14 Citations
AbstractAbstract PDF
Background

The epidermal growth factor receptor (EGFR) is a surrogate marker for basal-like breast cancer. A recent study suggested that EGFR may be used as a target for breast cancer treatment.

Methods

A total of 706 invasive ductal carcinomas (IDC) of the breast were immunophenotyped, and 82 cases with EGFR protein expression were studied for EGFR gene amplification.

Results

EGFR protein was expressed in 121 of 706 IDCs (17.1%); 5.9% were of luminal type, 25.3% of epidermal growth factor receptor 2 (HER-2) type, and 79.3% of basal-like tumors. EGFR gene amplification and high polysomy (fluorescent in situ hybridization [FISH]-positive) were found in 18 of 82 cases (22.0%); 41.2% of the HER-2+, EGFR+, cytokeratin 5/6- (CK5/6-) group, 11.2% of the HER-2-, EGFR+, CK5/6- group, and 19.1% of the HER-2-, EGFR+, CK5/6+ group. FISH-positive cases were detected in 8.3% of the EGFR protein 1+ expression cases, 15.9% of 2+ expression cases, and 38.5% of 3+ expression cases. In group 2, the tumors had a high Ki-67 labeling (>60%), but the patients showed better disease-free survival than those with tumors that co-expressed HER-2 or CK5/6.

Conclusions

EGFR-directed therapy can be considered in breast cancer patients with EGFR protein overexpression and gene amplification, and its therapeutic implication should be determined in HER-2 type breast cancer patients.

Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival
Soyoung Im, Hyun Joo Choi, Changyoung Yoo, Ji-Han Jung, Ye-Won Jeon, Young Jin Suh, Chang Suk Kang
Korean J Pathol. 2013;47(2):116-123.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.116
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  • 25 Citations
AbstractAbstract PDF
Background

The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established.

Methods

Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically.

Results

The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012).

Conclusions

Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.

No Detection of Simian Virus 40 in Malignant Mesothelioma in Korea
Minseob Eom, Jamshid Abdul-Ghafar, Sun-Mi Park, Joung Ho Han, Soon Won Hong, Kun Young Kwon, Eun Suk Ko, Lucia Kim, Wan Seop Kim, Seung Yeon Ha, Kyo Young Lee, Chang Hun Lee, Hye Kyoung Yoon, Yoo Duk Choi, Myoung Ja Chung, Soon-Hee Jung
Korean J Pathol. 2013;47(2):124-129.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.124
  • 7,271 View
  • 49 Download
  • 5 Citations
AbstractAbstract PDF
Background

Simian virus 40 (SV40), a polyomavirus, was discovered as a contaminant of a human polio vaccine in the 1960s. It is known that malignant mesothelioma (MM) is associated with SV40, and that the virus works as a cofactor to the carcinogenetic effects of asbestos. However, the reports about the correlation between SV40 and MM have not been consistent. The purpose of this study is to identify SV40 in MM tissue in Korea through detection of SV40 protein and DNA.

Methods

We analyzed 62 cases of available paraffin-blocks enrolled through the Korean Malignant Mesothelioma Surveillance System and performed immunohistochemistry for SV40 protein and real-time polymerase chain reaction (PCR) for SV40 DNA.

Results

Of 62 total cases, 40 had disease involving the pleura (64.5%), and 29 (46.8%) were found to be of the epithelioid subtype. Immunostaining demonstrated that all examined tissues were negative for SV40 protein. Sufficient DNA was extracted for real-time PCR analysis from 36 cases. Quantitative PCR of these samples showed no increase in SV40 transcript compared to the negative controls.

Conclusions

SV40 is not associated with the development of MM in Korea.

Prognostic Significance of BCL9 Expression in Hepatocellular Carcinoma
Jiyeon Hyeon, Soomin Ahn, Jae Jun Lee, Dae Hyun Song, Cheol-Keun Park
Korean J Pathol. 2013;47(2):130-136.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.130
  • 6,515 View
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  • 15 Citations
AbstractAbstract PDF
Background

BCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients.

Methods

We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months.

Results

Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078).

Conclusions

BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.

EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood
Mineui Hong, Young Hyeh Ko, Keon Hee Yoo, Hong Hoe Koo, Seok Jin Kim, Won Seog Kim, Heejung Park
Korean J Pathol. 2013;47(2):137-147.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.137
  • 11,351 View
  • 100 Download
  • 24 Citations
AbstractAbstract PDF
Background

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality.

Methods

Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed.

Results

STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis.

Conclusions

EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.

Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis
Miji Lee, Sung Bae Kim, Sang-wook Lee, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho
Korean J Pathol. 2013;47(2):148-157.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.148
  • 6,050 View
  • 47 Download
  • 3 Citations
AbstractAbstract PDF
Background

Human papillomavirus (HPV)-related tonsillar squamous cell carcinoma (TSCC) has recently been characterized as a distinct subset with a favorable prognosis. The prevalence and clinicopathologic significance of HPV-related TSCC in Koreans are not well known.

Methods

HPV in situ hybridization (ISH) accompanied by p53, p16, pRb, and cyclin D1 immunohistochemical staining were performed on 89 resection cases of TSCC from 2000 through 2010.

Results

HPV was detected by ISH in 59 of 89 cases (66.3%). HPV-positive TSCCs were more common in younger ages (p=0.005), and tumor sizes were smaller in the HPV-positive compared to the HPV-negative group (p=0.040). Positive HPV staining was significantly correlated with p16 expression (p<0.001), pRb inactivation (p=0.003), and cyclin D1 down-regulation (p<0.001) but not with p53 expression (p=0.334). Seventeen cases that showed p16-immunopositivity with HPV-negativity by ISH were retested by HPV typing; HPV DNA was not detected in all cases. There was no significant difference between HPV-positive and HPV-negative patients either in the disease-specific survival (DSS, p=0.857) or overall survival (p=0.910). Furthermore, pRb-inactivated cases showed better DSS (p=0.023), and p53-positive cases showed worse DSS (p=0.001).

Conclusions

Although high HPV prevalence was noted, it was not correlated with histopathologic findings or survival benefit. In addition to p53 expression, pRb inactivation along with p16 overexpression and down-regulation of cyclin D1 are thought to be important pathogenetic steps for developing TSCCs.

Case Studies
A Solitary Fibrous Tumor with Giant Cells in the Lacrimal Gland: A Case Study
Da Hye Son, Su Hyun Yoo, Ho-Seok Sa, Kyung-Ja Cho
Korean J Pathol. 2013;47(2):158-162.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.158
  • 5,959 View
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  • 6 Citations
AbstractAbstract PDF

Orbital solitary fibrous tumor (SFT) has recently been proposed as the encompassing terminology for hemangiopericytoma, giant cell angiofibroma (GCAF), and fibrous histiocytoma of the orbit. The lacrimal gland is a very rare location for both SFT and GCAF. A 39-year-old man presented with a painless left upper eyelid mass. An orbital computed tomography scan identified a 1.1 cm-sized well-defined nodule located in the left lacrimal gland. He underwent a mass excision. Histopathologic examination showed a proliferation of relatively uniform spindle cells with a patternless or focally storiform pattern. Dilated vessels were prominent, but angiectoid spaces lined with giant cells were absent. Floret-type giant cells were mostly scattered in the periphery. The tumor was immunoreactive for CD34 and CD99, but negative for smooth muscle actin and S-100 protein. This is the first Korean case of SFT of the lacrimal gland with overlapping features of GCAF, suggesting a close relationship between the two entities.

Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination
Go Eun Bae, Nara Yoon, Ha Young Park, Sang Yun Ha, Junhun Cho, Yunkyung Lee, Kyoung-Mee Kim, Cheol Keun Park
Korean J Pathol. 2013;47(2):163-166.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.163
  • 5,408 View
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  • 6 Citations
AbstractAbstract PDF

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.

Papillary Carcinoma of the Thyroid Gland with Nodular Fasciitis-like Stroma
Ki Yong Na, Hyun-Soo Kim, Ji-Youn Sung, Won Seo Park, Youn Wha Kim
Korean J Pathol. 2013;47(2):167-171.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.167
  • 7,292 View
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  • 10 Citations
AbstractAbstract PDF

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is a rare variant of PTC. The term 'PTC with fibromatosis-like stroma' has been used as a synonym to describe this variant. It is characterized by extensive proliferation of fibroblasts and myofibroblasts in the tumor stroma, which occurs in up to 80% of the tumors. We herein describe a case of PTC-NFS which developed in a 49-year-old woman with the demonstration of findings of ultrasonography, fine needle aspiration cytology and histological examination of the lesion. To characterize the stromal components, we investigated the expression of several immunohistochemical markers which have been shown to be expressed differently in nodular fasciitis (NF) and fibromatosis (FM). The immunostaining results demonstrated nuclear and cytoplasmic accumulation of β-catenin, cytoplasmic transforming growth factor-β expression and nuclear Smad expression in the stromal cells, suggesting that the stromal cells in this case have similar molecular profiles to those of FM rather than NF.

Congenital Peribronchial Myofibroblastic Tumor: A Case Study and Literature Review
Yuil Kim, Ha Young Park, Junhun Cho, Joungho Han, Eun Yoon Cho
Korean J Pathol. 2013;47(2):172-176.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.172
  • 6,085 View
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  • 6 Citations
AbstractAbstract PDF

Congenital peribronchial myofibroblastic tumor (CPMT) is a benign pulmonary spindle cell neoplasm of intrauterine and perinatal period, which is thought to arise from primitive peribronchial mesenchyme. We present a case detected incidentally in a one-month-old infant. The solid and partially necrotic tumor involved the right middle and lower lobes of the lung with extension to the diaphragm. Histologically, the tumor was composed of fasciculated monotonous spindle cells, proliferating peribronchiolar cartilage and round cells with rich vasculature, and high mitotic activity was identified in the round cell area. Immunohistochemical and electron microscopic studies showed that the spindle cells were myofibroblastic in phenotype. Although the tumor showed several malignant pathological features, recurrence was not observed in the two-year follow-up period, consistent with the benign clinical behavior of CPMT.

Extrapelvic Uterus-like Masses Presenting as Colonic Submucosal Tumor: A Case Study and Review of Literature
Ki Yong Na, Gou Young Kim, Kyu Yeoun Won, Hyun-Soo Kim, Sang Won Kim, Chi Hoon Lee, Jae Myung Cha
Korean J Pathol. 2013;47(2):177-181.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.177
  • 6,924 View
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  • 11 Citations
AbstractAbstract PDF

A uterus-like mass (ULM) is a central cavity lined by endometrial glands and stroma and surrounded by thick-walled smooth muscles. To date, 31 cases of ULM have been reported in the English literature. ULM typically presents as a single mass and is located in the pelvic cavity. We report here a very rare case of multiple extrapelvic ULMs involving the cecum, descending colon, and mesocolon. After extensive literature research, our case appears to be the first case of multiple ULMs found in extrapelvic sites and the first case of ULM in the colon. The present case suggests that ULM should be included in the differential diagnosis of colonic submucosal tumors in female patients with chronic abdominal pain or menstruation-associated symptoms.

ThinPrep Cytological Findings of Desmoplastic Small Round Cell Tumor with Extensive Glandular Differentiation: A Case Study
Hyun-Jung Kim, Byeong Seok Sohn, Ji-Eun Kwon, Jeong Yeon Kim, Kyeongmee Park
Korean J Pathol. 2013;47(2):182-187.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.182
  • 5,193 View
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  • 7 Citations
AbstractAbstract PDF

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive neoplasm. The cytological diagnosis of this tumor has only been reported in a few cases. In most of these cases, the diagnosis was made using fine-needle aspiration cytology. Most DSRCTs resemble disseminated carcinomatoses in their clinical manifestation as well as cytomorphologically, even in young-adult patients. These authors report a case of using peritoneal-washing and pleural-effusion ThinPrep cytology to diagnose DSRCT, with extensive glandular differentiation and mucin vacuoles. We found that fibrillary stromal fragment, clinical setting, and adjunctive immunocytochemical staining were most helpful for avoiding misdiagnosis.

Brief Case Report
Mucinous Non-neoplastic Cyst of the Pancreas
Jae Do Yang, Ji Soo Song, Sang Jae Noh, Woo Sung Moon
Korean J Pathol. 2013;47(2):188-190.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.188
  • 5,675 View
  • 38 Download
  • 5 Citations
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JPTM : Journal of Pathology and Translational Medicine