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ABSTRACT: Small intestinal adenocarcinomas (SIACs) are rare, and their molecular pathogenesis is largely unknown. To define the roles of E-cadherin and β-catenin, we performed immunohistochemistry for E-cadherin and β-catenin in 194 surgically resected SIACs with tissue microarrays and compared the data with clinicopathologic factors, including survival rates of patients with SIAC. Loss of E-cadherin expression and aberrant β-catenin expression were observed in 41.8% (81/194 cases) and 40.7% (79/194 cases) of SIACs, respectively. Combined loss of E-cadherin and aberrant β-catenin expression was observed in 24.2% (47/194 cases) of SIACs, and this feature was most frequently observed in mucinous adenocarcinomas and signet ring cell carcinomas (P < .001), poorly differentiated and undifferentiated carcinomas (P < .001), and tumors with advanced pT classification (P = .03). Survival times for patients with SIAC with both loss of E-cadherin and aberrant β-catenin expression (median, 13.9 months) were significantly shorter than those for patients without aberrant expression of both proteins (49.9 months), as determined by univariate (P < .001) and multivariate (P = .01) analyses. In conclusion, loss of E-cadherin and aberrant β-catenin expression correlate with poorly differentiated tumors, advanced T classification, and decreased patient survival time; therefore, it could be a prognostic factor in patients with SIAC.
American Journal of Clinical Pathology 02/2013; 139(2):167-76. · 2.60 Impact Factor
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ABSTRACT: 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.
The Korean Journal of Pathology 02/2013; 47(1):77-81. · 0.16 Impact Factor
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ABSTRACT: Laparoscopic Heller myotomy with antireflux procedure is considered to be a standard treatment for achalasia. Recently, peroral endoscopic myotomy (POEM) was developed and performed on patients with achalasia. However, there is no report on POEM use in South Korea. The aim of this study was to evaluate the technical feasibility of POEM in a porcine model.
POEM was performed on two mini pigs. We performed upper endoscopy under general anesthesia. A submucosal tunnel was created and the circular muscle layer was incised using several knives. The mucosal entry was closed using resolution clips. We performed a follow-up endoscopy and sacrificed the pigs 2 weeks after the POEM. The myotomy site was evaluated grossly and histologically.
POEM was successfully performed on the two mini pigs. No injuries to any abdominal or mediastinal structures occurred. Two weeks after the POEM, the esophageal mucosa healed without any endoscopic evidence of complications. Necropsy revealed that the circular muscle layer was completely lost and replaced with fibrotic tissue.
We found that POEM is a technically feasible method which can be performed on an animal model. However, to ensure safe use on patients with achalasia, further studies on technical methods and long-term follow-up examinations are required.
Clinical endoscopy. 01/2013; 46(1):54-8.
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ABSTRACT: Dietary restriction (DR) has many beneficial effects, but the detailed metabolic mechanism remains largely unresolved. As diet is essentially related to metabolism, we investigated the metabolite profiles of urines from control and DR animals using NMR and LC-Mass metabolomic approaches. Multivariate analysis presented distinctive metabolic profiles and marker signals from glucuronide and glycine conjugations pathways in the DR group. Broad profiling of the urine phase II metabolites with neutral loss scanning showed that glucuronide and glycine conjugation metabolites are generally higher in the DR group. The up-regulation of the phase II detoxifications in the DR group were confirmed by mRNA and protein expression levels of the UGT's and GLYAT's in actual liver tissues. Histopathology and serum biochemistry showed that the DR had beneficial effects of low serum ALT level and low glycogen granules in liver. In addition, the Nrf-2 signaling pathway was shown to be up-regulated, providing a mechanistic clue for the enhanced phase II detoxification in liver tissue. Taken together, our metabolomic and biochemical studies provide a possible metabolic perspective in understanding the complex mechanism of the beneficial effects of DR.
Molecular & Cellular Proteomics 12/2012; · 7.40 Impact Factor
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ABSTRACT: Advances of tissue microarray (TMA) technology have enabled simultaneous in situ analysis of biomarker expression in a large number of archived pathology specimens. However, the relatively high cost of TMA construction may hamper many researchers from using this essential tool of modern pathology research. We discuss methods for making TMA kits and recipient blocks for manual construction of high-density TMAs at low cost.
Ordinary cannula piercing needles, hypodermic needles, bone marrow biopsy needles, metallic ink cartridges of ballpoint pens, and disposable skin biopsy punches were used to construct self-made manual TMA kits. The recipient blocks were manufactured by boring holes in the conventional bare paraffin blocks. A mini electric hand drill and a microcompound table assembled on a drill stand were used to maximize the capacity of the recipient blocks.
By using TMA kits made from cannula piercing needles (16- and 18-gauge), it was possible to construct TMAs with 1 mm×140 cores, 0.6 mm×320 cores, 2 mm×70 cores, 3 mm×35 cores, and 5 mm×12 cores. The capacity of the recipient blocks could be dramatically increased by drilling holes.
Construction of TMAs using self-made TMA kits is an inexpensive alternative to construction of TMAs using commercial devices.
The Korean Journal of Pathology 12/2012; 46(6):562-8. · 0.16 Impact Factor
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ABSTRACT: Cancer registries play a fundamental role in cancer control and multicenter collaborative research. Recently, the need for reassessment of cancer registry criteria has arisen due to the newly released 2010 World Health Organization (WHO) classification. Accordingly, development of new coding guidelines for cancer is necessary to improve the quality of cancer registries, as well as to prevent conflicts that may arise when seeking medical insurance compensation.
With funding from the Management Center for Health Promotion, 35 members of the Gastrointestinal Pathology Study Group and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated in a second workshop for gastrointestinal tumor registration in Korea.
The topics of gastric epithelial tumor, colonic intramucosal carcinoma, neuroendocrine tumor (NET), gastrointestinal stromal tumor (GIST) and appendiceal mucinous tumor were discussed for new coding guidelines. A survey was then conducted among 208 members of the KSP for a consensus of the guidelines proposed in the workshop.
Although a few issues were set aside for further discussion, such as coding for non-gastric GIST and some types of NET, the members agreed upon most of the proposed guidelines. Therefore, we suggest using the newly revised International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) coding guidelines for registering gastrointestinal tumors in Korea.
Korean journal of pathology. 10/2012; 46(5):443-53.
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ABSTRACT: BACKGROUND: Small intestinal adenocarcinomas (SACs) are rare malignancies of the alimentary tract with uncertain carcinogenesis. METHODS: We investigated the expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically resected SACs, using tissue microarray technology. RESULTS: Twenty-four of the 188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0; 12.8%). Eighty-four and 31 cases were moderately and strongly positive, respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed that the expression of Smad4/DPC4 was related to an increased risk of lymphatic invasion but not to other clinicopathological features of the tumors (tumor location, differentiation, growth pattern, T stage, direct invasion, vascular invasion, and nodal metastasis). There was no significant association between Smad4/DPC4 expression and patient survival. CONCLUSIONS: The present research is the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with clinicopathologic correlation. Future studies should focus on the immunohistochemical and molecular characteristics of SACs to clarify their tumorigenesis.
Korean journal of pathology. 10/2012; 46(5):415-422.
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ABSTRACT: Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the ≤ 40 yr-old group and 261 cases of > 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.
Journal of Korean medical science 09/2012; 27(9):1027-36. · 0.84 Impact Factor
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Mee-Yon Cho, Joon Mee Kim,
Jin Hee Sohn,
Mi-Jung Kim,
Kyoung-Mee Kim,
Woo Ho Kim,
Hyunki Kim,
Myeong-Cherl Kook,
Do Youn Park,
Jae Hyuk Lee, [......],
Chang Ho Cho,
Moon-Il Park,
Yun Kyung Kang,
Youn Wha Kim,
Sun Och Yoon,
Han Ik Bae,
Mee Joo,
Woo Sung Moon,
Dae Young Kang,
Sei Jin Chang
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ABSTRACT: As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.
Cancer Research and Treatment 09/2012; 44(3):157-65.
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ABSTRACT: We report here a rare case of granular cell astrocytoma. A 75-year-old man was admitted to Inha University Hospital with a three-month history of language deterioration. In a magnetic resonance imaging, a 6.5 cm-sized heterogeneous enhancing mass was seen in both the frontal lobes and the anterior genu of the corpus callosum. A stereotactic biopsy was performed. The tumor was composed of large and small round cells with abundant intracytoplasmic granules. The nuclei were bland, round to oval, and often eccentrically located. The cytoplasm of the tumor cells was positive for glial fibrillary acidic protein and S-100 protein.
Korean journal of pathology. 08/2012; 46(4):370-2.
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ABSTRACT: Clusterin is known to be expressed in many human neoplasms, and is believed to participate in the regeneration, migration, and anti-apoptosis of tumor cells. However, few reports have addressed the relationship between the manifestation of clusterin and clinicopathologic parameters in pancreas cancer patients. In the present study, the authors investigated the expression of clusterin and its clinical significance in pancreatic adenocarcinoma.
Immunohistochemical staining was performed for clusterin in tumor tissues obtained from patients who received pancreatic resection with radical intent, and the associations of clusterin expression with various clinicopathologic parameters were analyzed in addition to the relation between its expression and survival.
Immunoreactivity for clusterin was observed in 17 of the 52 (33%) pancreatic adenocarcinomas examined. In addition, clusterin positivity was found to be associated with preoperative serum carcinoembryonic antigen level, perineural invasion, and, most strongly, lymph node metastasis. The survival analysis identified tumor differentiation and lymph node metastasis as the only significant prognostic factors.
Although not an independent prognostic factor, clusterin immunoreactivity can be used in conjunction with lymph node metastasis to predict survival in cases of pancreatic adenocarcinoma.
World Journal of Surgical Oncology 07/2012; 10:146. · 1.12 Impact Factor
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ABSTRACT: We report a case of gastritis cystica porfunda (GCP) associated with gastric carcinoma with lymphoid stroma (CLS). There was dysplastic change in the transitional area between GCP and CLS. Epstein-Barr virus (EBV) in situ hybridization (ISH) revealed positive reaction at the dysplastic area as well as at the CLS area. Immunohistochemical staining disclosed that dysplastic epithelium was similar to GCP in CK 20, MUC5AC, and E-cadherin expression, but similar to CLS in MUC6, CEA, p53, c-erb-B2, and EBV-ISH expression. Results of the EBV-ISH suggested that EBV infection may play a role in dysplastic change.
Pathology International 05/2012; 62(5):351-5. · 1.62 Impact Factor
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ABSTRACT: Silver nanoparticles (SNPs) have received considerable attention recently, because SNPs with different shapes and sizes exhibit
variable antimicrobial activity, which makes them useful for medical and hygienic purposes. SNPs have been detected in various
tissues and organisms after inhalation, oral ingestion, and contact with the skin, indicating that SNPs can be distributed
to different body tissues after uptake. Thus, the toxicity of SNPs to different body tissues after their uptake needs to be
studied. In this study, we performed a proteomic analysis of liver, lung, and kidney tissues in rats exposed to approximately
50 nm SNPs by intravascular injection. Then, the differentially expressed proteins representing a dose-dependent response
were identified. The differentially expressed proteins were mostly related to the known toxicity of SNPs, such as apoptosis,
increased reactive oxygen species, thrombus formation, and inflammation. Additionally, proteins related to metabolic disorders
including diabetes were identified as differentially expressed proteins in kidney, based solely on the analysis of the protein
profile and related disease pathway. In conclusion, the differentially expressed proteins identified in this study could provide
basic data for understanding the toxic and pathological responses of SNP-exposed tissues and to identify candidate SNP toxicity
biomarkers.
KeywordsSilver nanoparticle–Toxicoproteomics–Biomarker–Apoptosis–Reactive oxygen species–Blood coagulation
04/2012; 2(4):251-262.
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ABSTRACT: Today nanosciences are experiencing massive investment worldwide although research on toxicological aspect of these nano-sized
particles has just begun and to date, no clear guidelines exist to quantify the effects. In the present study, we focus on
silver nanoparticles, which represent one of the most widely investigated nanoparticles. The present data indicate that silver
nanoparticles seem to cross the cellular membrane of various tissues in Sprague Dawley rat and, therefore, might have an influence
on cell physiology and function. Rats are exposed via oral administration and intravenous injection with commercial silver
nanoparticles. Three types of silver nanoparticels are used in this study: 1) Type I, particle size 50–90 nm with no dispersant,
2) Type II, particle size 1–10 nm dispersed with several amino acids. After 4 weeks exposure we examined the clinical indicators
from blood and also analyzed histological changes in various tissues, including liver, kidney, and lung, to investigate the
histopathological changes. The concentration of 2 indicators, total cholesterol and creatinine were changed with statistical
importance. Also, lymphocytes/granulocyte ratio was significantly increased by silver nanoparticles. The histological change
had accordance with the change of clinical indicators. The inflammatory symptoms were observed in liver tissue and it lead
to the result that the hematologic/lymphocytic disorder, not hepatic disorder, would be related to silver nanoparticle toxicity.
Finally we propose 4 genes as size independent genomic biomarkers and 10 genes as representative biomarkers for histopathological
and clinical changes for silver nanoparticle exposure.
KeywordsSilver nanoparticle–Toxicogenomics–Biomarker
04/2012; 1(1):8-16.
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ABSTRACT: Clear cell adenocarcinoma of the urethra is a rare disease entity with an uncertain histogenesis. Here, we present a case of primary clear cell adenocarcinoma of the female urethra with its cytological findings. A 54-year-old woman presented with a painless gross hematuria lasting 3 months. On vaginal sonography, there was a sausage-like, elongated mass in the urethra, measuring 3.8×4.3 cm. The voided urine cytology revealed small clusters of rounded or papillary cells. The necrotic debris and inflammatory cells were present within some clusters of tumor cells. These tumor cells were enlarged and had abundant clear or granular cytoplasm with cytoplasmic vacuoles. The nucleus was granular and contained vesicular chromatin with prominent nucleoli. The hobnail cells and hyaline globules were also present as in a histologic section. The histologic findings were compatible with clear cell adenocarcinoma. The tumor showed distinctive cytological features. Cytologically, however, it is necessary to make a differential diagnosis from other adenocarcinoma or high-grade urothelial carcinoma.
Korean journal of pathology. 04/2012; 46(2):210-4.
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Mijin Gu,
Young Kyung Bae,
Ae Ri Kim,
Seung-Mo Hong,
Eunsil Yu,
Jihun Kim,
Kee-Taek Jang,
Hee-Kyung Chang,
Eun Sun Jung,
Han-Ik Bae, [......],
Young-Ha Oh,
Kyu Yun Jang,
Sun-Young Jun,
Dae Woon Eom,
Kye Won Kwon,
Gyeong Hoon Kang,
Jae Bok Park,
Soonwon Hong,
Soo Jin Jung,
Ji Shin Lee
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ABSTRACT: Background/Aims: Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC. Methodology: A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC). Results: The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status. Conclusions: The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).
Hepato-gastroenterology 03/2012; 59(119). · 0.66 Impact Factor
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ABSTRACT: A 74-year-old man suffered from jejunal perforation and adhesion to sigmoid colon due to adenocarcinoma associated with intraductal papillary mucinous neoplasm (IPMN) arising in a jejunal heterotopic pancreas. The jejunal lesion showed direct extension to the sigmoid colon, which was mistaken as sigmoid colon cancer by surgeons. Malignant transformation is a rare complication of a heterotopic pancreas. About half of malignancies in reported cases were ductal adenocarcinoma arising in the stomach, and the jejunal location is extremely rare. Furthermore, IPMN is also uncommon finding in a heterotopic pancreas.
Korean journal of pathology. 02/2012; 46(1):96-100.
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ABSTRACT: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. GISTs are predominant in the stomach and intestine, and rarely occur in the oesophagus. A GIST in the posterior mediastinum usually arises from the oesophagus, but single case of gastric GIST in the posterior mediastinum is reported. We present a case of a posterior mediastinal malignant GIST which was likely of gastric origin. The patient had no recurrence for 5 years after a complete resection.
Interactive cardiovascular and thoracic surgery 01/2012; 14(4):497-9.
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ABSTRACT: To evaluate the effectiveness of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses following BSRTC adoption.
According to the BSRTC, we reclassified cytologic samples originally diagnosed as 'indeterminate' with sequential surgical resection. Then, we analyzed the causes of cases, which were recategorized as 'atypia undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)'.
According to the BSRTC, 154 'indeterminate' cases were reclassified as follows: unsatisfactory, n = 5 (3.2%); benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular neoplasm, n = 7 (7.1%); suspicious for a Hürthle cell neoplasm, n = 4 (2.6%); suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC. Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In addition, papillary microcarcinoma and coexisting Hashimoto's thyroiditis caused inconclusive diagnoses.
The BSRTC can be easily applied to thyroid fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules into more detailed categories and thus reduce the number of cases classified as indeterminate. However, suboptimal preparation, papillary microcarcinoma, and coexisting Hashimoto's thyroiditis precluded cytopathologists from making definitive diagnoses.
Acta cytologica 01/2012; 56(2):122-9. · 0.49 Impact Factor
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Joon Mee Kim,
Mee-Yon Cho,
Jin Hee Sohn,
Dae Young Kang,
Cheol Keun Park,
Woo Ho Kim,
So-Young Jin,
Kyoung Mee Kim,
Hee Kyung Chang,
Eunsil Yu, [......],
Youn Wha Kim,
Do Youn Park,
Yun Kyung Kang,
Sun Hoo Park,
Hye Seung Han,
Young Bae Kim,
Ho Sung Park,
Yang Seok Chae,
Kye Won Kwon,
Hee Jin Chang
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ABSTRACT: The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important, but the diagnostic criteria, terminology, and grading system are not the same in the East and West. A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists, but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion. Although the Vienna classification was introduced to reduce diagnostic discrepancies, it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions. Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine. Japan is geographically close to Korea, and academic exchanges are active. Additionally, Korean doctors are familiar with Western style medical terminology. As a result, the terminology, definitions, and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea. To solve this problem, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis: (1) a diagnosis of carcinoma is based on invasion; (2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching, budding, or marked glandular crowding; (3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts, the lesion is considered high grade dysplasia; (4) if severe cytologic atypia is present, careful inspection for invasive foci is necessary, because the risk for invasion is very high; and (5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern, papillae, ridges, vesicular nuclei, high nuclear/cytoplasmic ratio, loss of nuclear polarity, thick and irregular nuclear membrane, and nucleoli.
World Journal of Gastroenterology 06/2011; 17(21):2602-10. · 2.47 Impact Factor
