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Volume 44(2); April 2010
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Review Article
Legal and Ethical Consideration in the Use of Human Biological Material.
Youngjoon Ryu, Bongkyung Shin, Baek Hui Kim, Aeree Kim, Hankyeom Kim
Korean J Pathol. 2010;44(2):111-116.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.111
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AbstractAbstract PDF
Traditionally, pathologists have used human biological material primarily for diagnostic purposes. More recently, advances in biomedical technology and changes in the research environment have placed new demands on pathologists and their handling of human materials. Moreover, these technological advances have required pathologists to be not only experts in diagnosis, but also managers of biobanks storing human biological material. Consequently, pathologists might now be confronted with unanticipated legal and ethical questions. We investigated seven examples of South Korean legislation concerning human biological material, including "The Bioethics and Safety Act" (2005), and we considered possible conflicts of interest between donors and researchers. We also reviewed international bioethical guidelines and legal precedents from several countries with special regard to pathologic glass slides, paraffin blocks, remaining specimens and other guidelines. We conclude that a better understanding of the legal and ethical questions concerning human biological material leads pathologists to safer and more conscientious management of these samples.
Original Articles
Korean Pediatric/Adolescent Lymphoma: Incidence and Pathologic Characteristics.
Seung Sook Lee, Jin Man Kim, Young Hyeh Ko, Jooryung Huh, Chang Suk Kang, Chul Woo Kim, Yun Kyung Kang, Jai Hyang Go, Min Kyung Kim, Wan Seop Kim, Yoon Jung Kim, Hyun Jung Kim, Hee Kyung Kim, Jong Hee Nam, Hyung Bae Moon, Chan Kum Park, Tae In Park, Young Ha Oh, Dong Wha Lee, Jong Sil Lee, Juhie Lee, Hyekyung Lee, Sung Chul Lim, Kyu Yun Jang, Hee Kyung Chang, Yoon Kyung Jeon, Hye Ra Jung, Min Sun Cho, Hee Jeong Cha, Suk Jin Choi, Jae Ho Han, Sook Hee Hong, Insun Kim
Korean J Pathol. 2010;44(2):117-124.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.117
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AbstractAbstract PDF
BACKGROUND
The Hematopathology Study Group of the Korean Society of Pathologists conducted a nation-wide retrospective analysis of Korean pediatric lymphoma, to provide pathologic data on pediatric/adolescent lymphoma subtypes and features.
METHODS
All lymphoma cases of all age groups were collected during a recent 2 year-period (2005-2006) from 32 institutes in Korea. Among 3,686 lymphoma patients, 142 who were age 18 or less were classified according to the World Health Organization (WHO) classification.
RESULTS
Among 142 pediatric/adolescent lymphoma patients, Hodgkin lymphoma accounted for 21 (14.8%) and non-Hodgkin lymphoma (NHL) for 121 (85.2%). Hodgkin lymphoma appears to be more common in the pediatric/adolescent age group than in the all-ages group (14.8% vs 4.4%). T- and natural killer cell-NHL was more common in the pediatric/adolescent age group than in the all ages group (46.3% vs 22%). The majority of Korean pediatric/adolescent NHL cases was composed of Burkitt lymphoma, T- or B-lymphoblastic lymphoma, anaplastic large-cell lymphoma, and diffuse large B-cell lymphoma. For lymphoma patients under the age of 6 years, most had B-lymphoblastic or Burkitt lymphoma, which commonly presented at extranodal sites.
CONCLUSIONS
The distribution of lymphoma subtypes in the pediatric/adolescent age group is quite different from the distribution of adults, but it was quite similar to distribution in Western countries.
Lyn Expression in Osteoblastic Osteosarcoma Tissues and Its Correlation with Clinicopathologic Factors.
Min Sun Jin, Shin Kwang Khang, Min Suk Kim, Hee Seung Choi, Jung Eun Lee, Kil Ho Kim, Dae Geun Jeon, Jae Soo Koh
Korean J Pathol. 2010;44(2):125-131.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.125
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AbstractAbstract PDF
BACKGROUND
The Src family kinases (SFKs) are involved in multiple aspects of tumorigenesis, such as, proliferation, migration, and angiogenesis, and are involved in the generation and progression of many types of tumors. Furthermore, dasatinib, a general SFKs inhibitor was recently approved for use in chronic myeloid leukemia. This study was performed to evaluate the expression of Lyn, a member of the SFKs, in osteosarcoma tissues.
METHODS
One hundred and sixteen patients with osteoblastic osteosarcoma were selected for Lyn expression analysis. The correlation between Lyn expression in tumor sections and patients' clinicopathologic characteristics and the prognostic significance of Lyn expression were evaluated.
RESULTS
Lyn was found to be expressed in 52 of the 116 patients (44.8%), and Lyn positive tumor was found to be significantly associated with a lytic tumor pattern on plain radiographs (p = 0.04). Furthermore, those positive for Lyn showed longer metastasis free survival (5-year metastasis free survival, 65.2% for Lyn positive and 46.8% for Lyn negative; p = 0.06), though this was only marginally significant.
CONCLUSIONS
Lyn was found to be overexpressed in osteosarcoma tissues, and this overexpression was found to be correlated with osteolysis.
Frequency of Intrahepatic FoxP3+ Regulatory T cells during the Natural Course of Chronic Hepatitis B: An Immunohistochemical Study Using Needle-Biopsied Liver Tissue.
Ji Yoon Bae, Hyung Kyung Kim, Hanna Kang, Ha Rin Cheong, Dong Eun Song, Sun Hee Sung, Heasoo Koo, Woon Sup Han, Jeong Kyong Lee, Tae Hun Kim, Kyu Won Chung, Min Sun Cho
Korean J Pathol. 2010;44(2):132-140.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.132
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AbstractAbstract PDF
BACKGROUND
Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized.
METHODS
Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry.
RESULTS
The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load.
CONCLUSIONS
FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.
Usefulness of DOG1 Expression in the Diagnosis of Gastrointestinal Stromal Tumors.
Jun Mo Kim, Aeri Kim, Joon Hyuk Choi, Young Kyung Bae
Korean J Pathol. 2010;44(2):141-148.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.141
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AbstractAbstract PDF
BACKGROUND
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Expression of KIT protein (CD117) is an important diagnostic criterion of GIST. However, about 5% of GISTs are CD117 negative. Discovered on GIST 1 (DOG1) was introduced recently as a promising marker for GIST. We tested this new antibody in 105 GISTs tissue specimens, including 6 cases of metastatic GISTs, to determine the usefulness of DOG1 expression in the diagnosis of GISTs.
METHODS
We performed immunohistochemical (IHC) staining for DOG1 and CD117 on tissue microarrays that included 70 gastric GISTs, 29 small intestinal GISTs, 6 metastatic GISTs, 14 gastric leiomyomas and 16 gastric schwannomas.
RESULTS
DOG1 was positive in 98.1% (103/105) of GISTs and CD117 was positive in 97.1% (102/105) of GISTs. Only 1 case was negative for both markers. Two (66.7%) out of 3 GISTs tested CD117 negative were tested DOG1 positive. All leiomyomas and schwannomas were negative for both DOG1 and CD117.
CONCLUSIONS
DOG1 was highly expressed in GIST including CD117 negative cases. Adding DOG1 testing to the IHC panel for diagnosing GIST will help to identify GIST patients who are CD117 negative but may otherwise benefit from targeted therapy.
The Prognostic Implications of Cystic Change in Clear Cell Renal Cell Carcinoma.
Heae Surng Park, Eun Jung Jung, Jae Kyung Myung, Kyung Chul Moon
Korean J Pathol. 2010;44(2):149-154.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.149
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  • 4 Citations
AbstractAbstract PDF
BACKGROUND
Cystic renal cell carcinoma has been reported to have a good prognosis. However, previous studies included cases of multilocular cystic renal cell carcinoma, which has an excellent prognosis, and renal cell carcinoma with cystic necrosis, which has an adverse prognosis. Therefore, we analyzed the prognostic influence of cystic change in clear cell renal cell carcinoma after excluding those morphological features.
METHODS
We identified 225 patients with clear cell renal cell carcinoma who underwent nephrectomy between 2001 and 2003. The clinicopathologic features were compared with clinical outcomes.
RESULTS
Cystic change in clear cell renal cell carcinoma (n = 66) was significantly associated with younger patient age (< 55), smaller tumor size (< or = 4 cm), lower pT stage (pT1, T2), M0 stage at initial diagnosis, lower tumor, node, and metastasis stage (I, II), and lower nuclear grade (1, 2). Patients with cystic change in clear cell renal cell carcinoma had significantly longer cancer-specific (p = 0.015) and progression-free survival (p = 0.004) than those without cystic change, by univariate analysis. Multivariate analysis revealed that cystic change significantly decreased the risk of cancer progression (risk ratio, 0.27; 95% confidence interval, 0.11 to 0.69).
CONCLUSIONS
In patients with clear cell renal cell carcinoma, cystic change is a good independent predictor for survival.
Diagnostic Utility of AMACR and Claudin-7 for the Classification of Renal Cell Carcinoma.
Sang Hwa Shim, Mee Joo, Han Seong Kim, Sun Hee Chang, Ki Young Kwon
Korean J Pathol. 2010;44(2):155-161.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.155
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AbstractAbstract PDF
BACKGROUND
The histologic classification of renal cell carcinoma (RCC) is based on the cytoarchitectural features, yet sometimes this requires correlation with the immunophenotype. Alpha-methylacyl-CoA racemase (AMACR) and claudin-7 have recently been introduced as useful markers that are frequently expressed in papillary RCC (PRCC) and chromophobe RCC (ChRCC), respectively. The aims of this study are to evaluate the expressions of AMACR and claudin-7 in RCCs and to investigate whether they are helpful for making the histological classification of RCCs.
METHODS
Immunohistochemistry for CD10, RCC marker, cytokeratin (CK)7, CD117, AMACR and claudin-7 was performed for 104 RCCs, and these consisted of 54 clear cell RCCs (CCRCC), 26 PRCCs and 24 ChRCCs.
RESULTS
For diagnosing PRCC, the sensitivity and specificity of AMACR were 92.3% and 71.8%, respectively, and using AMACR(+)/CK7(+), the specificity was increased by 23.1% to 94.9%. For diagnosing ChRCC, the sensitivity and specificity of claudin-7 were 91.7% and 78.8%, respectively, and using claudin-7(+)/AMACR(-), the specificity was significantly improved (to 96.3%). For diagnosing CCRCC, CK7(-)/claudin-7(-)/CD117(-) was the most useful immunohistochemical panel (sensitivity, 96.3%; specificity, 98%).
CONCLUSIONS
AMACR and claudin-7 are helpful markers for the histologic classification of RCCs, and their diagnostic utility is strengthened when they are used as an immunohistochemical panel, AMACR(+)/CK7(+) for PRCC, claudin-7(+)/AMACR(-) for ChRCC and CK7(-)/claudin-7(-)/CD117(-) for CCRCC.
Histopathological Evaluation of Pediatric Intestinal Pseudo-Obstruction: Quantitative Morphometric Analysis of Pathological Changes in the Enteric Nervous System.
Hyung Kyung Kim, Harin Cheong, Hanna Kang, Ji Yoon Bae, Dong Eun Song, Min Sun Cho, Sun Hee Sung, Woon Sup Han, Heasoo Koo
Korean J Pathol. 2010;44(2):162-172.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.162
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AbstractAbstract PDF
BACKGROUND
This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis.
METHODS
We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC).
RESULTS
Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group.
CONCLUSIONS
Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.
An Approach to Diagnosing Gastrointestinal Stromal Tumors Using Immunohistochemistry of c-kit and PDGFRA with Molecular Analysis.
Jeong Shik Kim, Jae Hoon Kim, Hyun Jin Oh, In Soo Suh, Jong Gwang Kim, Byung Wook Kang, Wan Sik Yu, Ho Young Chung, Han Ik Bae
Korean J Pathol. 2010;44(2):173-178.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.173
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AbstractAbstract PDF
BACKGROUND
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis.
METHODS
We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues.
RESULTS
Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11.
CONCLUSIONS
Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.
Aberrant Promoter Methylation of the Vimentin Gene in Colorectal Cancer Associated with the Adenoma-Carcinoma Sequence.
Mi Hee Cho, Yu Mi Lee, Jin Sook Kim, Hyun Soo Kim, Kyung Hwa Lee, Sang Woo Juhng, Jae Hyuk Lee
Korean J Pathol. 2010;44(2):179-186.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.179
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AbstractAbstract PDF
BACKGROUND
DNA hypermethylation is a common epigenetic finding in human cancers and is closely associated with transcriptional silencing. In the present study, we investigated the proportion of colorectal neoplasms that showed the adenoma-carcinoma progression and vimentin gene methylation.
METHODS
Methylation status of the vimentin gene was examined in nontumoral mucosa, adenomas, and adenocarcinomas from 45 colorectal cancer patients who had adenoma and adenocarcinoma together. Methylation status was determined by bisulfite modification and the methylation-specific polymerase chain reaction. The expression of the vimentin gene product was also examined by immunohistochemistry.
RESULTS
Promoter methylation of vimentin was detected in 80% (36 out of 45 cases) of adenocarcinomas, 82.2% (37 of 45) of adenomas, and 28.9% (13 of 45) of normal epithelia, and the difference between neoplastic and normal specimens was statistically significant (p < 0.001). However, no significant correlations were observed between methylation frequency and clinicopathologic variables. Immunohistochemically, vimentin expression was not observed in either normal epithelial cells or tumor cells. Protein expression and vimentin promoter methylation were not associated.
CONCLUSIONS
The frequency of aberrant methylation of the vimentin gene was high in colonic adenomas and adenocarcinomas. This result suggests that the methylation status of vimentin may be clinically beneficial in screening for colorectal cancer patients and may be helpful in clarifying colorectal cancer biology.
The Expression of Apolipoprotein D in Hepatocellular Carcinoma.
Hongxiu Han, Chan Kum Park
Korean J Pathol. 2010;44(2):187-190.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.187
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AbstractAbstract PDF
BACKGROUND
Apolipoprotein D (Apo D) has recently been identified as a novel tumor suppressor gene. Apo D may have a profound effect on the carcinogenesis and progression of hepatocellular carcinoma. This study was designed to evaluate the expression of Apo D in hepatocellular carcinoma and to investigate the relationship between the expression of Apo D and the clinicopathological characteristics and the patients' survival.
METHODS
An immunohistochemical study was performed on the tumors and tissues from 43 hepatocellular carcinoma (HCC) patients with controls to determine the expression of Apo D protein.
RESULTS
Our data showed that a higher expression of Apo D was seen in 10 of 43 cases (23.3%), while a lower and no expression of Apo D was observed in 28 of 43 cases (65.1%) and 5 of 43 cases (11.6%), respectively. A reduced expression of Apo D was correlated with the tumor stage (p = 0.037) and tumor size (p = 0.017). However, the patients' 5-year survival was not associated with the expression of Apo D (p = 0.903).
CONCLUSIONS
The results suggest that a reduced Apo D protein expression may play an important role in HCC progression as associated with the tumor stage and size, but it does not affect the survival of HCC patients.
Galectin-3 Expression and BRAF Mutation in Cases of Cytologically Suspicious Papillary Thyroid Carcinoma.
Dokyung Kim, Hyunki Kim, Jinyoung Kwak, Minju Kim, Hyung Jae Jung, Ja Seung Koo, Beom Jin Lim, Chankwon Jung, SoonWon Hong
Korean J Pathol. 2010;44(2):191-198.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.191
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AbstractAbstract PDF
BACKGROUND
Fine needle aspiration, which is known as the most accurate and cost-effective method for diagnosis of thyroid nodule, still may result in indeterminate cases that are pauci-cellular and show minor nuclear atypia, but most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs and galectin-3 was expressed by malignant tumors, helping us to differentiate malignancies from benign lesions.
METHODS
Cases studied included histologically 44 confirmed PTC cases and 18 benign cases previously diagnosed as suspicious of PTC using cytologic examination. Cases were analyzed for galectin-3 expression by immunohistochemical staining and BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme.
RESULTS
All 44 cases of PTC and 8 of 18 benign controls expressed galectin-3. BRAF mutations were found in only 9 of the 44 PTC cases. Assessment of galectin-3 expression demonstrated high sensitivity but low specificity. Evaluation of BRAF mutation revealed high specificity and low sensitivity.
CONCLUSIONS
This study suggests that the combined application of these two methods for PTC of suspicious cytology is complementary.
Case Reports
A Case of Paraduodenal Pancreatitis and Immunohistochemical Analysis.
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hyung Sik Shin, Joo Seop Kim, Doo Jin Kim
Korean J Pathol. 2010;44(2):199-203.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.199
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AbstractAbstract PDF
Paraduodenal pancreatitis (PP) is a rare, distinct form of chronic pancreatitis, and it is related to alcohol abuse in middle-aged men. A 36-year-old man with a history of chronic recurrent pancreatitis for 4 years and alcohol abuse for 15 years presented with abdominal pain. Computed tomography revealed a multilocular cystic mass 3.2 x 3 x 3 cm in size and it was located within the muscular layer of the duodenal wall. The cysts were lined by a single layer of eosinophilic cuboidal epithelial cells that stained positively for mucin (MUC)1, MUC6, cytokeratin (CK)7 and CK19 and they stained negatively for MUC2, MUC5AC and CK5/6. Mild, chronic inflammatory reaction around the cystic wall, Brunner's gland hyperplasia and several clusters of heterotopic pancreatic tissue were noted. We report here on a case of PP and we demonstrated that the pancreatitis was of pancreatic ductal cell origin according to the MUC and CK expression patterns we observed on the immunohistochemical analysis.
Completely Isolated Enteric Duplication Cyst Presenting as an Inguinal Hernia.
Jung Uee Lee, Jong Ok Kim, Say June Kim, Hye Jung Sul
Korean J Pathol. 2010;44(2):204-206.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.204
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  • 4 Citations
AbstractAbstract PDF
Enteric duplication cysts are uncommon congenital anomalies whose embryogenesis remains unknown. We report here on an isolated enteric duplication cyst, that presents as an inguinal hernia. A 21-year-old woman was admitted with a month-long history of a palpable mass in the left groin. Radiologically, a computed tomography scan revealed a 3.5 x 2.5 cm sized cystic mass in subcutaneous layers of the left suprapubic area. Microscopically, the cystic wall resembled gut wall. The wall was composed of two distinct muscle layers with the presence of Auerbach's plexus. On examining the entire sections of the cyst wall very carefully, no epithelial lining was found on the inner surface. The submucosa was slightly fibrotic. The diagnosis was a completely isolated enteric duplication cyst.
Complex Bronchopulmonary Foregut Malformation: Extralobar Pulmonary Sequestration Communicating with an Esophageal Duplication Cyst: A Case Report.
Soyoung Im, Sun Mi Lee, Ji Han Jung, Jinyoung Yoo, Kyu Do Cho, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2010;44(2):207-210.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.207
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AbstractAbstract PDF
We report here on a case of a rare, complex bronchopulmonary foregut malformation (BPFM) that was composed of an extralobar pulmonary sequestration communicating with an esophageal duplication cyst. A 33-year-old female presented with an incidentally detected chest mass. The computed tomography revealed a 7.5 x 4.0 cm sized heterogeneous, solid and cystic lesion in the right superior mediastinum. Surgical resection demonstrated the solid portion to be isolated lung tissue invested in its own pleura. A unilocular cyst was communicating with the bronchus of the sequestrated lung, and microscopically the cyst was lined by squamous epithelium overlying the thick layers of smooth muscle. This case is important for understanding the spectrum of BPFMs and for differentiating a mediastinal mass, especially one at the unusual location.

JPTM : Journal of Pathology and Translational Medicine