Although microscopic analysis of tissue slides has been the basis for disease diagnosis for decades, intra- and inter-observer variabilities remain issues to be resolved. The recent introduction of digital scanners has allowed for using deep learning in the analysis of tissue images because many whole slide images (WSIs) are accessible to researchers. In the present study, we investigated the possibility of a deep learning-based, fully automated, computer-aided diagnosis system with WSIs from a stomach adenocarcinoma dataset. Three different convolutional neural network architectures were tested to determine the better architecture for tissue classifier. Each network was trained to classify small tissue patches into normal or tumor. Based on the patch-level classification, tumor probability heatmaps can be overlaid on tissue images. We observed three different tissue patterns, including clear normal, clear tumor and ambiguous cases. We suggest that longer inspection time can be assigned to ambiguous cases compared to clear normal cases, increasing the accuracy and efficiency of histopathologic diagnosis by pre-evaluating the status of the WSIs. When the classifier was tested with completely different WSI dataset, the performance was not optimal because of the different tissue preparation quality. By including a small amount of data from the new dataset for training, the performance for the new dataset was much enhanced. These results indicated that WSI dataset should include tissues prepared from many different preparation conditions to construct a generalized tissue classifier. Thus, multi-national/multi-center dataset should be built for the application of deep learning in the real world medical practice.
Adenocarcinoma ; Classification ; Dataset ; Diagnosis ; Learning ; Observer Variation ; Stomach

Gastrointestinal neoplasms with an exocrine and a neuroendocrine component are rare. Such neoplasms are called “mixed adenoneuroendocrine carcinomas” (MANECs) according to the most recent World Health Organization classification of gastrointestinal tract neoplasms. MANECs have no specific findings that distinguish them from pure adenocarcinomas. In addition, the optimal management strategy of MANECs is largely unknown. We describe the case of a 32-year-old man with dizziness and abdominal bloating. A cecal mass was suspected based on an image study done at a local clinic. We evaluated the cecal mass by using colonoscopy, contrast enhanced computed tomography of the abdomen, positron emission tomography-computed tomography, and laboratory studies. The patient underwent a right hemicolectomy and adjuvant chemotherapy. The final histopathological diagnosis was a high-grade MANEC of the ascending colon, tumor stage T3N2M0.
Abdomen ; Adenocarcinoma ; Adult ; Cecum* ; Chemotherapy, Adjuvant ; Classification ; Colon, Ascending ; Colonoscopy ; Diagnosis ; Dizziness ; Electrons ; Gastrointestinal Neoplasms ; Gastrointestinal Tract ; Humans ; World Health Organization

OBJECTIVETo investigate the prognostic factors of patients with lymph node-negative metastasis gastric cancer (pN0).

METHODSClinicopathological data of patients with pN0 gastric cancer who underwent radical operation at the Department of Surgical Oncology, The First Hospital of China Medical University from May 1980 to August 2012 were collected and analyzed retrospectively.

INCLUSION CRITERIA(1) Patients were diagnosed as gastric adenocarcinoma; (2) Postoperative pathology confirmed T1a to 4bN0M0 gastric cancer; (3) Total number of harvested lymph node was more than 15. The patients, who died within 1 month after the operation, died of other diseases, had remnant gastric cancer, or had incomplete follow-up data, were excluded. Univariate analysis was used to analyze the clinical factors that may influence the prognosis of patients with stage pN0 gastric cancer, then, those significant variables were entered into the Cox's proportional hazards regression model for multivariate analysis to obtain the independent prognostic factors for patients with pN0 gastric cancer finally. Furthermore, the prognosis of patients with pN0 advanced gastric cancer (invasive depth ≥ T2) were analyzed using the same method.

RESULTSA total of 610 patients with pN0 gastric cancer were enrolled in the study, including 441 males and 169 females with age ranging from 19 to 83 (mean 56.4±11.0) years, D1 lymph node dissection in 45 cases, D2 lymph node dissection in 543 cases, D3 lymph node dissection in 22 cases, and 384 cases of advanced gastric cancer. The overall followed-up was 1 to 372 (median 32) months. Ninety cases (14.8%) were dead during the follow-up. The median survival was 277.7(95%CI: 257.6 to 297.8) months, and the 1-, 3-, 5-year survival rates were 96.5%, 87%, 83.2%. Univariate analysis showed that tumor diameter, depth of invasion, gross type, lymph node dissection and lymph vessel cancer embolus were related to the prognosis (all P<0.05). The 5-year survival rate of patients with tumor diameter >4 cm was significantly lower than those with tumor diameter ≤4 cm (75.6% vs. 87.8%, P=0.000). The 5-year survival rates of T1a, T1b, T2, T3 and T4 were 98.4%, 92.8%, 84.2%, 61.0% and 31.4% respectively, and the difference was statistically significant (P=0.000). In gross type, 5-year survival rate of early gastric cancer was 96.0%, and of Borrmann I( to IIII( type gastric cancer was 100%, 83.4%, 73.7% and 68.9% respectively, whose difference was statistically significant(P=0.000). The 5-year survival rates in patients undergoing lymph node dissection D1, D2 and D3 were 100%, 83.3% and 58.7%, and the difference was significant (P=0.005). The 5-year survival rate of patients with positive lymphatic cancer embolus was lower than those with negative ones (69.4% vs. 86.9%, P=0.000). Multivariate analysis showed that the gross type [Borrmann II(/early gastric cancer: HR(95% CI)=15.129(3.284 to 69.699), Borrmann III(/early gastric cancer: HR(95% CI)=14.613 (3.292 to 64.875), Borrmann IIII(/early gastric cancer: HR (95% CI)=15.430 (2.778 to 85.718),Borrmann IIIII(/early gastric cancer: HR(95%CI)=12.604 (1.055 to 150.642), P=0.025] and the positive lymphatic cancer embolus [HR(95% CI)=3.241 (2.056 to 5.108), P=0.000] were the independent prognostic factors of patients with pN0 gastric cancer. For pN0 patients with advanced gastric cancer, multivariate analysis showed that the depth of invasion [stage T3/stage T2: HR(95%CI)=1.520 (0.888 to 2.601), stage T4/stage T2: HR(95%CI)=2.235(1.227 to 4.070); P=0.031] and the positive lymphatic cancer embolus [HR(95%CI)=3.065 (1.930 to 4.868); P=0.000] were the independent risk factors influencing the prognosis.

CONCLUSIONSPositive lymphatic cancer embolus and worse gross pattern indicate poorer prognosis of patients with pN0 gastric cancer, which may be used as effective markers in evaluating the prognosis. As for pN0 advanced gastric cancer, invasion depth and positive lymphatic cancer embolus can play a more important role in the prediction.

Adenocarcinoma ; classification ; diagnosis ; mortality ; Adult ; Aged ; Aged, 80 and over ; China ; Female ; Humans ; Lymph Node Excision ; statistics & numerical data ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; physiopathology ; Lymphatic Vessels ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; pathology ; physiopathology ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; classification ; diagnosis ; mortality ; Survival Rate

OBJECTIVETo investigate neuroendocrine differentiation and Wilms' tumor protein-1 (WT-1) expression in breast mucinous carcinoma and their clinicopathological significance.

METHODSThe clinicopathological data of 65 patients with breast mucinous carcinoma, including 31 cases of mixed mucinous carcinoma, 23 cases of hypocellular pure mucinous carcinoma and 11 cases of hypercellular pure mucinous carcinoma, admitted in Taizhou Hospital from January 2010 to June 2015 were retrospectively reviewed. The expression of neuroendocrine markers and WT-1 was detected by immunohistochemistry staining in all cases.

RESULTSThe mixed mucinous carcinomas and hypercelluar pure mucinous carcinomas had higher incidence of axillary lymph node metastasis and human epidermal recepter 2 (HER-2) positive than hypocellular pure mucinous carcinoma (all (P<0.01). However, the difference was not significant between mixed mucinous carcinomas and hypercellular pure mucinous carcinomas (all P>0.05). The expression of neuroendocrine marker was stronger in hypercellular mucinous carcinoma than that in mixed mucinous carcinoma and hypocellular mucinous carcinoma (all (P<0.05), but the difference was not statistically significant between mixed mucinous carcinoma and hypocellular pure mucinous carcinoma (P>0.05). The expression of WT-1 was weaker in mixed mucinous carcinoma than that in hypercellular and hypocellular pure mucinous carcinoma(all (P<0.05), but the difference was not statistically significant between hypercellular and hypocellular pure mucinous carcinoma (P>0.05). The mucinous carcinomas with lymph node metastasis had lower expression of neuroendocrine markers than those without lymph node metastasis ((P<0.01). The expression of WT-1 in breast mucinous carcinoma with lymph node metastasis trended lower than that in those without lymph node metastasis, but the difference was not statistically significant (P>0.05).

CONCLUSIONHypercellular pure mucinous breast carcinoma has higher rates of lymph node metastasis and HER-2 amplification than hypocellular pure mucinous carcinoma, the sub-classification of breast pure mucinous carcinoma should be considered. Neuroendocrine differentiation and WT-1 expression may be helpful in distinguishing the subtypes of breast mucinous carcinoma. Breast mucinous carcinoma with neuroendocrine differentiation trends to have less lymph node metastasis.

Adenocarcinoma, Mucinous ; classification ; diagnosis ; pathology ; Axilla ; Breast Neoplasms ; classification ; diagnosis ; pathology ; Female ; Humans ; Immunohistochemistry ; Incidence ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neuroendocrine Tumors ; diagnosis ; pathology ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; WT1 Proteins ; metabolism

BACKGROUND: Since 2003, the Korean Society of Pathologists (KSP) has been officially providing medical advisory services (MAS). We reviewed the cases submitted to the KSP between 2003 and 2014. METHODS: In total, 1,950 cases were submitted, most by private health insurance companies. The main purposes of the consultations were to clarify the initial diagnoses and to assign a proper disease classification code. We comprehensively reviewed 1,803 consultation cases with detailed information. RESULTS: In spite of some fluctuations, the number of submitted cases has been significantly increasing over the 12 study years. The colon and rectum (40.3%), urinary bladder (14.2%), and stomach (6.9%) were the three most common tissues of origin. The most common diagnoses for each of the three tissues of origin were neuroendocrine tumor (50.7%), non-invasive papillary urothelial carcinoma (70.7%), and adenocarcinoma (36.2%). Regardless of the tissue of origin, neuroendocrine tumor of the digestive system was the most common diagnosis (419 of 1,803). CONCLUSIONS: In the current study, we found that pathologic consultations associated with private health insurance accounted for a large proportion of the MAS. Coding of the biologic behavior of diseases was the main issue of the consultations. In spite of the effort of the KSP to set proper guidelines for coding and classification of tumors, this review revealed that problems still exist and will continue to be an important issue.
Adenocarcinoma ; Classification ; Clinical Coding ; Colon ; Consultants* ; Diagnosis ; Digestive System ; Humans ; Insurance, Health ; Neuroendocrine Tumors ; Rectum ; Referral and Consultation ; Stomach ; Urinary Bladder

BACKGROUNDS/AIMS: Gallbladder perforation is a rare but potentially fatal disease. We herein present our clinical experience in diagnosis and management of 32 cases of gallbladder perforation. METHODS: This retrospective study was conducted with inclusion of all cases of gallbladder perforation that presented to our hospital from January 2012 to November 2014. Cases of traumatic gallbladder perforation and patients younger than 12 years of age were excluded from this study. RESULTS: This study included 32 patients (13 males and 19 females). The mean age of patients was 55.9 years. Gallbladder perforation was most common in the 5th and 6th decade of life. The mean age of patients with type I, II, and III gallbladder perforation was 57.0 years, 57.6 years, and 49.8 years, respectively. The most common site of perforation was the fundus, followed by the body and Hartmann's pouch (24 : 5 : 2). Most of the type I gallbladder perforations were diagnosed intraoperatively, type II gallbladder perforations were diagnosed by enhanced abdominal computed tomography, and type III gallbladder perforations were diagnosed during laparoscopic cholecystectomy converted to open cholecystectomy for cholelithiasis. Mortality was highest in patients with type I gallbladder perforation. The mean hospital stay was 10.1 days, 6.4 days, and 9.2 days in patients with type I, II, and III gallbladder perforation, respectively. The histopathologic analysis in 28 patients who were operated on showed acute cholecystitis in 19 cases, acute-on-chronic cholecystitis in 4 cases, chronic cholecystitis in 4 cases, and mucinous adenocarcinoma of the gallbladder in a single case. CONCLUSIONS: Gallbladder perforation represents a special diagnostic and surgical challenge. Appropriate classification and management are essential.
Adenocarcinoma, Mucinous ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Cholecystitis ; Cholecystitis, Acute ; Cholelithiasis ; Classification ; Diagnosis ; Gallbladder* ; Humans ; Length of Stay ; Male ; Mortality ; Retrospective Studies

Adenocarcinoma, Follicular ; classification ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Carcinoma, Papillary ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Signal Transduction ; Thyroid Neoplasms ; classification ; metabolism ; pathology

Adenocarcinoma, Follicular ; classification ; diagnosis ; pathology ; Carcinoma, Papillary ; diagnosis ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Thyroid Neoplasms ; diagnosis ; pathology ; surgery

Adenocarcinoma, Follicular ; metabolism ; pathology ; Adenoma, Chromophobe ; metabolism ; pathology ; Adenoma, Oxyphilic ; metabolism ; pathology ; Angiomyoma ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Carcinoma, Papillary ; metabolism ; pathology ; Carcinoma, Renal Cell ; classification ; metabolism ; pathology ; ultrastructure ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; classification ; metabolism ; pathology ; ultrastructure ; Thyroid Neoplasms ; metabolism ; pathology

Adenocarcinoma, Clear Cell ; metabolism ; pathology ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; Carcinoma, Endometrioid ; metabolism ; pathology ; Carcinoma, Transitional Cell ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Neoplasms, Glandular and Epithelial ; classification ; metabolism ; pathology ; Ovarian Neoplasms ; classification ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism ; WT1 Proteins ; metabolism