Porphyromonas gingivalis predicts local recurrence after endoscopic submucosal dissection of early esophageal squamous cell carcinoma or precancerous lesion.

BACKGROUND: Porphyromonas gingivalis plays an oncogenic role in development and progression of esophageal squamous cell carcinoma (ESCC). However, the impact of P. gingivalis on local recurrence of early ESCC or precancerous lesion after ESD treatment remains unknown. The present study aimed to evaluate the impact of P. gingivalis on local recurrence after ESD treatment of early ESCC or high-grade dysplasia (HGD). METHODS: The amount of P. gingivalis was assessed by immunohistochemistry in 205 patients with early ESCC or HGD. Univariate and multivariate Cox regression analyses were performed to determine the effect of P. gingivalis on local recurrence. Propensity score matching analysis was performed to reduce the imbalance of baseline characteristics. A nomogram integrating significant prognostic factors was built for local recurrence prediction. RESULTS: The amount of P. gingivalis increased significantly in neoplasms that invaded up to muscularis mucosa and submucosa compared with lesions confined to epithelium or lamina propria. Overabundance of P. gingivalis was positively associated with invasion depth, post-ESD stricture and local recurrence. Univariate and multivariate Cox regression analyses revealed that P. gingivalis, longitudinal length of lesion and lymphovascular invasion were independent predictors for post-ESD recurrence. A nomogram comprising P. gingivalis, lymphovascular involvement, and lesion length performed well for prediction of post-ESD local recurrence with the concordance indices of 0.72 (95%CI, 0.62 to 0.80), 0.72 (95%CI, 0.63 to 0.80), and 0.74 (95%CI, 0.65 to 0.83) in the validation cohort, the entire cohort, and the subcohort after PSM, respectively. CONCLUSION: P. gingivalis overabundance is a risk factor and a potential predictor for local recurrence of early ESCC or HGD after ESD treatment. Thus, clearance of P. gingivalis represents an attractive strategy for prognosis improvement and for prevention of ESCC.

Efficacy and safety of additional surgery after non-curative endoscopic submucosal dissection for early colorectal cancer.

BACKGROUND: Additional surgery is recommended when early colorectal cancer (ECRC) is resected by non-curative endoscopic submucosal dissection (ESD) and there is significant risk of lymph node metastasis (LNM). The aim of this study was to investigate the efficacy and safety of additional surgery after non-curative ESD for ECRC and evaluate long-term outcomes. METHODS: Patients with ECRC who underwent ESD and additional surgery between July 2007 and November 2013 were identified. Histology and patient data were collected during an average period of more than 5 years to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis. RESULTS: Fifty-one patients who underwent additional surgery were eligible for analysis. Overall, regional LNM was detected in 5 patients (9.8%) and presence of lymphovascular infiltration was a significant risk factor. Surgery-related complications occurred in 3 patients (5.9%). During a median follow-up period of 59 months, no metastasis or local recurrence was observed. Three patients died of other diseases and no CRC-related deaths took place. CONCLUSIONS: Additional surgery after non-curative ESD for ECRC is effective and safe and should be encouraged to foster curative treatment and better long-term outcomes.

Identification and validation of dysregulated MAPK7 (ERK5) as a novel oncogenic target in squamous cell lung and esophageal carcinoma.

BACKGROUND: MAPK7/ERK5 (extracellular-signal-regulated kinase 5) functions within a canonical three-tiered MAPK (mitogen activated protein kinase) signaling cascade comprising MEK (MAPK/ERK kinase) 5, MEKK(MEK kinase) 2/3 and ERK5 itself. Despite being the least well studied of the MAPK-modules, evidence supports a role for MAPK7-signaling in the pathology of several cancer types. METHODS AND RESULTS: Fluorescence in situ hybridization (FISH) analysis identified MAPK7 gene amplification in 4% (3/74) of non-small cell lung cancers (NSCLC) (enriched to 6% (3/49) in squamous cell carcinoma) and 2% (2/95) of squamous esophageal cancers (sqEC). Immunohistochemical (IHC) analysis revealed a good correlation between MAPK7 gene amplification and protein expression. MAPK7 was validated as a proliferative oncogenic driver by performing in vitro siRNA knockdown of MAPK7 in tumor cell lines. Finally, a novel MEK5/MAPK7 co-transfected HEK293 cell line was developed and used for routine cell-based pharmacodynamic screening. Phosphorylation antibody microarray analysis also identified novel downstream pharmacodynamic (PD) biomarkers of MAPK7 kinase inhibition in tumor cells (pMEF2A and pMEF2D). CONCLUSIONS: Together, these data highlight a broader role for dysregulated MAPK7 in driving tumorigenesis within niche populations of highly prevalent tumor types, and describe current efforts in establishing a robust drug discovery screening cascade.

Two microRNA panels to discriminate three subtypes of lung carcinoma in bronchial brushing specimens.

RATIONALE: Effective treatment for lung cancer requires accuracy in subclassification of carcinoma subtypes. OBJECTIVES: To identify microRNAs in bronchial brushing specimens for discriminating small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC) and for further differentiating squamous cell carcinoma (SQ) from adenocarcinoma (AC). METHODS: Microarrays were used to screen 723 microRNAs in laser-captured, microdissected cancer cells from 82 snap-frozen surgical lung specimens. Quantitative reverse-transcriptase polymerase chain reaction was performed on 153 macrodissected formalin-fixed, paraffin-embedded (FFPE) surgical lung specimens to evaluate seven microRNA candidates discovered from microarrays. Two microRNA panels were constructed on the basis of a training cohort (n = 85) and validated using an independent cohort (n = 68). The microRNA panels were applied as differentiators of SCLC from NSCLC and of SQ from AC in 207 bronchial brushing specimens. MEASUREMENTS AND MAIN RESULTS: Two microRNA panels yielded high diagnostic accuracy in discriminating SCLC from NSCLC (miR-29a and miR-375; area under the curve [AUC], 0.991 and 0.982 for training and validation data set, respectively) and in differentiating SQ from AC (miR-205 and miR-34a; AUC, 0.977 and 0.982 for training and validation data set, respectively) in FFPE surgical lung specimens. Moreover, the microRNA panels accurately differentiated SCLC from NSCLC (AUC, 0.947) and SQ from AC (AUC, 0.962) in bronchial brushing specimens. CONCLUSIONS: We found two microRNA panels that accurately discriminated between the three subtypes of lung carcinoma in bronchial brushing specimens. The identified microRNA panels may have considerable clinical value in differential diagnosis and optimizing treatment strategies based on lung cancer subtypes.

[Screening of differentially expressed microRNAs in borderline and malignant gastrointestinal stromal tumors].

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs. METHODS: Six GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples. RESULTS: Direct comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR. CONCLUSIONS: The differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.

Prognostic value of preoperative CT features for disease-free survival in patients with primary gastric gastrointestinal stromal tumors after resection.

PURPOSE: Tumor size is an important prognostic factor without consideration of the necrotic and cystic components within tumor for patients with gastrointestinal stromal tumors (GISTs). We aimed to extract the enhancing viable component from the tumor using computed tomography (CT) post-processing software and evaluate the value of preoperative CT features for predicting the disease-free survival (DFS) after curative resection for patients with primary gastric GISTs. METHODS: 132 Patients with primary gastric GISTs who underwent preoperative contrast-enhanced CT and curative resection were retrospectively analyzed. We used a certain CT attenuation of 30 HU to extract the enhancing tissue component from the tumor. Enhancing tissue volume and other CT features were assessed on venous-phase images. We evaluated the value of preoperative CT features for predicting the DFS after surgery. Univariate and multivariate Cox regression analyses were performed to find the independent risk factor for predicting the DFS. RESULTS: Of the 132 patients, 68 were males and 64 were females, with a mean age of 61 years. The median follow-up duration was 60 months, and 28 patients experienced disease recurrence and distant metastasis during the follow-up period. Serosal invasion (p < 0.001; HR = 5.277) and enhancing tissue volume (p = 0.005; HR = 1.447) were the independent risk factors for predicting the DFS after curative resection for patients with primary gastric GISTs. CONCLUSION: Preoperative contrast-enhanced CT could be useful for predicting the DFS after the surgery of gastric GISTs, and serosal invasion and enhancing tissue volume were the independent risk factors.

Prognostic analysis of combined curative resection of the stomach and liver lesions in 30 gastric cancer patients with synchronous liver metastases.

BACKGROUND: Gastric cancer with synchronous liver metastasis remains a clinical treatment challenge. There has been a longstanding debate on the question whether surgical resection could be beneficial to long-term survival. This study is to investigate the effectiveness and prognostic factors of combined curative resection of the stomach and liver lesions in gastric cancer patients with synchronous liver metastases. METHODS: A total of 30 patients who underwent simultaneous curative gastric and liver resection from March 2003 to April 2008 were analyzed retrospectively. Univariate and multivariate analyses were performed to select independent factors for survival. RESULTS: The overall 1-, 2-, 3- and 5-year survival rates of 30 patients were 43.3%, 30.0%, 16.7% and 16.7%, respectively, with a median survival of 11.0 months and 5 patients still living by the time of last follow-up. Single liver metastasis (p=0.028) and an absence of peritoneal dissemination (p=0.007) were significantly independent prognostic factors for these gastric cancer patients with synchronous liver metastases. Major adverse events were protracted stomach paralysis in 2 patients and pulmonary infection in another 2 patients, all of whom recovered after conservative treatment. CONCLUSIONS: This descriptive study without control group found that patients with solitary liver metastasis and absence of peritoneal dissemination could have better survival benefit from simultaneous curative resection of the gastric cancer and liver metastases.

[Staging and histologic grading of gastrointestinal stromal tumors].

OBJECTIVE: To investigate the clinical stage and histological grade of gastrointestinal stromal tumors. METHODS: Twelve clinical and pathological parameters were assessed in 613 patients with follow-up information. These parameters were classified into two gross spread parameters including liver metastasis and peritoneal dissemination, five microscopic spread parameters including lymph node metastasis, vascular, fat, nerve and mucosal infiltration, and five histological parameters including mitotic count ≥ 10 per 50 high-power fields, muscularis propria infiltration, coagulative necrosis, perivascular pattern and severe nuclear atypia. RESULTS: The accumulated 5-year disease-free survival (DFS) and overall survival (OS) of 293 patients without any of these predictive parameters of malignancy were 99.3% and 100.0%, respectively. They were regarded as nonmalignant and further evaluations on the stage and grade of these tumors were not performed. At least one and at most seven predictive parameters of malignancy were identified in 320 patients. For these patients, the accumulated 5-year DFS and OS rates were 43.9% (mean 6.7 years) and 59.7% (mean 9.3 years), respectively. The DFS showed significant difference between patients with and without gross spread (P < 0.01), with and without microscopic spread (P = 0.001). DFS and OS were associated with the number of predictive parameters of malignancy in patients without gross spread (P < 0.01 for both DFS and OS), but not in patients with gross spread (P = 0.882 and 0.441, respectively). CONCLUSIONS: Malignant GIST could be divided into clinical stages I and II based on the absence and presence of gross spread, respectively. The degree of malignancy of patients in clinical stage I could be graded according to the number of predictive parameters of malignancy. Patients in clinical stage II were of the highest degree of malignancy regardless of the number of parameters. The staging and grading of gastrointestinal stromal tumors in this study are strongly associated with prognosis.

[Detection of KRAS gene mutation and its clinical significance in colorectal adenocarcinoma].

OBJECTIVE: To explore the clinical significance of KRAS mutation detection in colorectal adenocarcinoma. METHODS: Paraffin-embedded tissue specimens were obtained from 440 patients with colorectal adenocarcinoma. The genomic DNA was extracted. Mutations of exon 2 of KRAS gene were examined by PCR and direct sequencing. RESULTS: Somatic mutations of KRAS gene were identified in 146 cases, with the mutation rate of 33.2% (146/440). Among these 146 patients, KRAS mutation involved codon 12 in 118 patients, including 35G > A (Gly12Asp, 62 cases), 35G > T (Gly12Val, 35 cases), 34G > T (Gly12Cys, 9 cases), 34G > A (Gly12Ser, 6 cases), 35G > C (Gly12Ala, 5 cases), and 34G > C (Gly12Arg, 1 case); in 27 patients the mutation involved codon 13, including 38G > A (Gly13Asp, 25 cases), 38G > C (Gly13 Val, 1 case) and 37G > T (Gly13 Cys, 1 case); and in one patient, the mutation involved codon 14 with 40G > A (Val14Ile). The status of KRAS or codon 12 mutations in colorectal adenocarcinoma was related to patients' gender (P = 0.021 and P = 0.030, respectively), and this significant correlation to females was conserved in clinical stage III (P = 0.007 and P = 0.003, respectively), but not in stages I, II, and IV. The status of KRAS or codon 12 mutations was also related to tumor stage. Between stage II and stage IV, the mutation rate of KRAS and codon 12 showed significant difference (P = 0.028 and 0.034, respectively). Between stage III and stage IV, only the codon 12 mutation rate showed significant difference (P = 0.011). Codon 13 mutation was not related to tumor stage. CONCLUSION: About one third of patients with colorectal adenocarcinoma have KRAS gene mutation, which might be related to patients' gender; and could be consistently detected by PCR and direct sequencing.

Familial gastrointestinal stromal tumors with KIT germline mutation in a Chinese family: A case report.

BACKGROUND: Familial gastrointestinal stromal tumors (GISTs) is a rare autosomal dominant disorder characterized by an array of clinical manifestations. Only 35 kindreds with germline KIT mutations and six with germline PDGFRA mutations have been reported so far. It is often characterized by a series of manifestations, such as multiple lesions and hyperpigmentation. However, the effect of imatinib treatment in these patients is still uncertain. CASE SUMMARY: Here, we report two patients (father and daughter) in a Chinese family (for the first time) with germline KIT mutation, and described their pathology, genetics and clinical manifestations. A 25-year-old Chinese woman went to hospital because of abdominal pain, and computed tomography showed multiple tumors in the small intestine. Small pigmented spots appeared on the skin within a few months after birth. Her father also had multiple pigmented spots and a history of multifocal GISTs. Multiple GISTs associated with diffuse interstitial Cajal cells (ICCs) hyperplasia were positive for CD117 and DOG-1. Gene sequencing revealed a germline mutation at codon 560 of exon 11 (p.V560G) of KIT gene in these two patients. Imatinib therapy showed the long-lasting disease stability after resection. Remarkably, the hypopigmentation of the skin could also be observed. Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient. CONCLUSION: Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT/PDGFRA mutation, hyperpigmentation and family history.

Anlotinib plus Epirubicin Followed by Anlotinib Maintenance as First-line Treatment for Advanced Soft-tissue Sarcoma: An Open-label, Single-arm, Phase II Trial.

PURPOSE: The treatment outcome for locally advanced or metastatic soft-tissue sarcoma (STS) remains unsatisfactory. Anlotinib had demonstrated impressive activity in the subsequent-line treatment of STS. This study investigated the combination of anlotinib and epirubicin followed by anlotinib maintenance as first-line treatment for patients with advanced STS. PATIENTS AND METHODS: This prospective, open-label, single-arm, phase II trial was conducted in Zhongshan Hospital, Fudan University. Eligible patients were ages 18 years or older and had previously untreated, pathologically confirmed, unresectable locally advanced or metastatic STS. All patients received up to six cycles of anlotinib plus epirubicin followed by anlotinib maintenance until disease progression, unacceptable toxicity, or death. The primary endpoint was the progression-free survival (PFS) rate at 6 months. The study was registered on chictr.org (identifier ChiCTR1900024928). RESULTS: From June 2019 to August 2020, 30 patients were enrolled. By December 2021, the median PFS was 11.5 months [95% confidence interval (CI): 8.6-14.4 months], while the median overall survival was not reached (95% CI: NE-NE). The objective response rate was 13.33% and the disease control rate was 80.0%. The most common adverse events (AE) included anemia (43.3%), nausea/vomiting (40.0%), fatigue (36.7%), leukopenia (30.0%), and proteinuria (10.0%), which were mainly of grade 1 or 2. The most frequent grade 3 or 4 AEs were anemia (10.0%), febrile neutropenia (33.3%), hypothyroidism (3.3%), and leukopenia (3.3%). No treatment-related death occurred. CONCLUSIONS: The combination of anlotinib and epirubicin followed by anlotinib maintenance demonstrated promising efficacy with a favorable safety profile.

Exploring pathological signatures for predicting the recurrence of early-stage hepatocellular carcinoma based on deep learning.

Background: Postoperative recurrence impedes the curability of early-stage hepatocellular carcinoma (E-HCC). We aimed to establish a novel recurrence-related pathological prognosticator with artificial intelligence, and investigate the relationship between pathological features and the local immunological microenvironment. Methods: A total of 576 whole-slide images (WSIs) were collected from 547 patients with E-HCC in the Zhongshan cohort, which was randomly divided into a training cohort and a validation cohort. The external validation cohort comprised 147 Tumor Node Metastasis (TNM) stage I patients from The Cancer Genome Atlas (TCGA) database. Six types of HCC tissues were identified by a weakly supervised convolutional neural network. A recurrence-related histological score (HS) was constructed and validated. The correlation between immune microenvironment and HS was evaluated through extensive immunohistochemical data. Results: The overall classification accuracy of HCC tissues was 94.17%. The C-indexes of HS in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that the HS (HR= 4.05, 95% CI: 3.40-4.84) was an independent predictor for recurrence-free survival. Patients in HS high-risk group had elevated preoperative alpha-fetoprotein levels, poorer tumor differentiation and a higher proportion of microvascular invasion. The immunohistochemistry data linked the HS to local immune cell infiltration. HS was positively correlated with the expression level of peritumoral CD14+ cells (p= 0.013), and negatively with the intratumoral CD8+ cells (p< 0.001). Conclusions: The study established a novel histological score that predicted short-term and long-term recurrence for E-HCCs using deep learning, which could facilitate clinical decision making in recurrence prediction and management.

Two-step artificial intelligence system for endoscopic gastric biopsy improves the diagnostic accuracy of pathologists.

Background: Endoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS). Methods: The EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance. Results: The average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00). Conclusions: The EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists.

[Role of heterogeneous nuclear ribonucleoprotein A2/B1 protein in the pathogenesis of non-small cell lung cancer].

OBJECTIVE: To study the expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) in non-small cell lung cancer (NSCLC), and the interaction between hnRNP A2/B1 protein and mRNA of DNA repair enzymes O(6)-methylguanine DNA-methyltransferase (MGMT), 8-oxoguanine DNA glycosylase (OGG1), redox factor 1(Ref-1), DNA-dependent protein kinase (including DNA-PKcs and ku). METHODS: The expression and distribution of hnRNP A2/B1 were detected by immunohistochemistry and Western blot on 50 NSCLC samples from patients who underwent resection in Zhongshan Hospital. The hnRNP A2/B1 mRNA expression was tested by real-time PCR. Co-immunoprecipitation (co-IP) combined RT-PCR was used to investigate whether hnRNP A2/B1 could be bound with the mRNA of the above mentioned 5 DNA repair enzymes in human lung cancer cell line (HTB-182). Then immunohistochemistry and real-time PCR were used to detect the expression of MGMT in the same group of patients. RESULTS: HnRNP A2/B1 protein and mRNA expressions were increased in the NSCLC tissues than that in the corresponding normal lung tissues. HnRNP A2/B1 was expressed predominantly in the nuclei of tumor cells. The positive rate and immunohistochemistry score of hnRNP A2/B1 in tumor tissue were significantly higher than that in normal tissue (P < 0.01). In stage III-IV NSCLC, hnRNP A2/B1 expression was higher than that in stage I-II. There was no significant differences of hnRNP A2/B1 expression among patients of different age, sex, histological type, and smoking history. The results of co-IP combined RT-PCR suggested that hnRNP A2/B1 is bound with MGMT mRNA, and MGMT expression is decreased in tumor tissue of NSCLC. CONCLUSIONS: The results of this study show that hnRNP A2/B1 protein and mRNA are highly expressed in NSCLC, and hnRNP A2/B1 is bound with MGMT mRNA, which indicate that it might be one of the mechanisms of hnRNP A2/B1 participating in the pathogenesis of NSCLC.

[Focal nodular hyperplasia of liver: a clinicopathologic study of 238 patients].

OBJECTIVE: To study the clinicopathologic features of focal nodular hyperplasia (FNH) of liver. METHODS: The clinical, radiologic, pathologic findings and follow-up data of 238 cases of FNH were retrospectively analyzed. RESULTS: The patients included 93 females and 145 males. The age of the patients ranged from 11 to 77 years (median = 39.1 years). Amongst the 233 patients who had clinical information available, 188 were asymptomatic, 216 had no history of hepatitis B and/or C infection and 232 had negative serum alpha-fetoprotein level. Amongst the 185 patients who had undergone radiologic examination, 123 (66.5%) were accurately diagnosed as such. Macroscopically, of the 284 lesions from 238 patients, the average diameter was 3.7 cm. Two hundred and fifteen cases (90.3%) were solitary, 172 cases were located in the right lobe and 115(40.5%) had central stellate fibrotic scars or lobulated cut surface. Histologically, 229 lesions belonged to classic type and 9 lesions were of non-classic type. The latter was further classified as the telangiectatic form (6 lesions) and the mixed hyperplastic and adenomatous form (3 lesions). There was no evidence of significant cytologic atypia. Follow-up data were available in 173 patients (72.7%). None of them died of the disease and 2 patients suffered from relapses after 2 and 4 years, respectively. CONCLUSIONS: FNH is a hyperplastic response of normal liver cells to local blood flow anomalies. It has no obvious sex predilection and more than 66% can be diagnosed accurately with radiologic examination. The lesions in the current study show no cytologic atypia.

Primary central nervous system Burkitt lymphoma as concomitant lesions in the third and the left ventricles: a case study and literature review.

This study reports the case of a 75-year-old woman with intermittent speech disturbance, headache, and general malaise. Brain magnetic resonance imaging showed a double lesion located in the third ventricle and temporal horn of the lateral ventricle. We completely removed the lesion in the third ventricle, adhering to the septum pellucidum. The histopathological diagnosis was Burkitt lymphoma, which was confirmed to be primary in postoperative investigation. To our knowledge, this is the first case of primary Burkitt lymphoma involving cerebral ventricles. Finally, we reviewed the characteristics of primary central nervous system Burkitt lymphoma.

[Melanotic epithelioid clear cell tumor of kidney: report of three cases].

OBJECTIVE: To study the pathologic features and immunophenotype of 3 cases of melanotic epithelioid clear cell tumor of kidney. METHODS: More than 2000 cases of renal tumors were retrospectively reviewed. Three cases of melanotic epithelioid clear cell tumor were identified. Immunohistochemical study was carried out using the paraffin-embedded tissue samples. Electron microscopy was also performed in 1 case. RESULTS: Amongst the 3 cases studied, the male-to-female ratio is 1:2. Histologically, 2 cases showed a clear cell carcinoma-like pattern. Papillary structures covered by clear cells and eosinophilic cells were observed in 1 case. Immunohistochemical study showed that the tumor cells in all cases expressed HMB 45. Two of them were also positive for Melan A. The staining for epithelial markers and S-100 protein was negative. Melanosomes were not identified by ultrastructural examination. CONCLUSIONS: Melanotic epithelioid clear cell tumor is a rarely seen neoplasm of kidney. There are some histologic overlaps with renal cell carcinoma, epithelioid angiomyolipoma and melanoma. Immunohistochemical study is useful in confirming the diagnosis. The tumor represents a morphologic variant of epithelioid angiomyolipoma.

[Study on clinicopathologic parameters of malignant behavior in gastrointestinal stromal tumors].

OBJECTIVE: To determinate the clinicopathologic parameters in predicting the malignant behavior of gastrointestinal stromal tumor (GIST). METHODS: Eight hundred and forty cases of GIST were retrospectively reviewed. The tumors were classified as malignant if they met any of the following criteria: evidence of gross dissemination (including liver metastasis and/or peritoneal spread), evidence of microscopic dissemination (including lymph node metastasis, infiltration to vessels, fat tissue, nerves and/or mucosal tissue), or disease relapse. The remaining cases were provisionally classified as tumors of uncertain biologic behavior. A number of morphologic parameters were then evaluated under light microscopy and univariate and multivariate analyses were adopted for this study. RESULTS: Histologic findings correlated with evidences of the following morphologic parameters were considered in accord with the criteria of the malignant behavior: mitotic count>or=10 per 50 high-power fields (P<0.01), muscle infiltration (P<0.01), coagulative necrosis (P<0.01), perivascular growth pattern (P=0.005) and remarkable nuclear atypia (P=0.014). Basing on the above criterion, 485 cases were re-classified as "malignant" and 355 cases "non-malignant". Follow-up data showed that the five-year disease-free survival and overall survival in the "non-malignant" group were 99.3% and 100% respectively, in contrast to 43.9% and 59.7% respectively in the "malignant" group (P<0.01). CONCLUSIONS: The set of clinicopathologic parameters is useful in predicting the malignant behavior of GIST and prognosis.

Author Correction: G9a regulates breast cancer growth by modulating iron homeostasis through the repression of ferroxidase hephaestin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.