Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours.

AIMS: MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumours. MED12 has not been genotyped in most other gynaecological mesenchymal tumours. The purpose of this study was to determine the prevalence of MED12 mutations in uncommon gynaecological mesenchymal tumours. METHODS AND RESULTS: Sixty-eight uncommon gynaecological mesenchymal tumours were genotyped for MED12 exon 2, including 27 Müllerian adenosarcomas (including three tentatively diagnosed as 'variant adenosarcomas'), six cellular angiofibromas, six aggressive angiomyxomas, five angiomyofibroblastomas, five superficial myofibroblastomas, five atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas. Immunohistochemistry for CD10, myogenic markers, hormone receptors, MDM2, and CDK4, and fluorescence in-situ hybridization (FISH) for JAZF1, PHF1 and YWHAE rearrangement, were performed on selected cases. The three 'variant adenosarcomas' harboured MED12 exon 2 mutations (including p.L36R hotspot mutation, recurrent p.L39_A50del, and a novel splice site mutation). Three endometrial stromal sarcomas with JAZF1-SUZ12 or JAZF1-PHF1 fusion harboured unprecedented mutations (p.D54G in two, and p.Q48* in one). All remaining tumours were wild-type. The three MED12-mutated 'variant adenosarcomas' showed distinctive morphological features, including 'fibromyomatous' cytomorphology, a close association with adenomyosis, clustered thick-walled vessels, focal conspicuous hyalinization, and intralymphovascular tumour growth. Features of conventional adenosarcomas, including nuclear atypia, mitotic activity, periglandular condensation, and phyllodes-like architecture, were inconspicuous. All three cases showed immunoreactivity for desmin and hormone receptors, while being negative for MDM2 and CDK4; they showed no JAZF1, PHF1 or YWHAE rearrangement. Despite deep myoinvasion, these tumours followed an indolent clinical course. CONCLUSIONS: These MED12-mutated adenosarcoma-like tumours might represent a distinct entity that requires more studies for its identification. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours.

Neuroimaging and quality-of-life outcomes in patients with brain metastasis and peritumoral edema who undergo Gamma Knife surgery.

OBJECT: Gamma Knife surgery (GKS) has been shown to be effective for treating many patients with brain metastasis. Some brain metastases demonstrate significant peritumoral edema; radiation may induce cerebral edema or worsening preexisting edema. This study was conducted to evaluate the imaging and neurobehavioral outcomes in patients with preexisting peritumoral edema who then undergo GKS. METHODS: Between August 2003 and January 2008, 63 cases of brain metastasis with significant peritumoral edema (> 20 cm(3)) were prospectively studied. The study inclusion criteria were as follows: 1) a single metastatic lesion with significant edema (perilesional edema signal volume on FLAIR > 20 cm(3)); and 2) inclusion of only 1 lesion > 20 cm(3) in the study (in cases of multiple lesions noted on FLAIR images). All patients received MR imaging with pulse sequences including T1-weighted imaging and FLAIR with or without contrast and T2-weighted imaging at an interval of 3 months. A neurological assessment and Brain Cancer Module (BCM-20) questionnaire were obtained every 2-3 months. Kaplan-Meier, Cox regression, and logistic regression were used for analysis of survival and associated factors. RESULTS: At the time of GKS, the median Karnofsky Performance Scale (KPS) score was 70 (range 50-90), and the mean BCM-20 score was 45.5 +/- 6.1. The mean tumor volume (+/- standard deviation) was 5.2 +/- 4.6 cm(3) with corresponding T2-weighted imaging and FLAIR volumes of 59.25 +/- 37.3 and 62.1 +/- 38.8 cm(3), respectively (R(2) = 0.977, p < 0.001). The mean edema index (volume of peritumoral edema/tumor volume) was 17.5 +/- 14.5. The mean peripheral and maximum GKS doses were 17.4 +/- 2.3 and 35 +/- 4.7 Gy, respectively. The median survival was 11 months. The longer survival was related to KPS scores >or= 70 (p = 0.008), age < 65 years (p = 0.022), and a reduction of > 6 in BCM-20 score (p = 0.007), but survival was not related to preexisting edema or tumor volume. A reduction in BCM-20 score of > 6 was related to decreased volume in T1-weighted and FLAIR imaging (p < 0.001). Thirty-eight (79.2%) of 48 patients demonstrated decreased tumor volume and accompanied by decreased T2-weighted imaging and FLAIR volume. Eight (16.7%) of the 48 patients exhibited increased or stable tumor volume. A margin dose > 18 Gy was more likely to afford tumor reduction and resolution of peritumoral edema (p = 0.005 and p = 0.006, respectively). However, prior external-beam radiation therapy correlated with worsened preexisting peritumoral edema (p = 0.013) and longer maintenance of corticosteroids (p < 0.001). CONCLUSIONS: Patients demonstrating a reduction in the BCM-20 score > 6, age < 65 years, and KPS score >or= 70 exhibited longer survival. Significant preexisting edema did not influence the tumor response or clinical outcome. The resolution of edema was related to better quality of life but not to longer survival.

Therapy conversion to biphasic insulin aspart 30 improves long-term outcomes and reduces the costs of type 2 diabetes in Saudi Arabia.

OBJECTIVE: An observational study in Saudi Arabia indicated that conversion to biphasic insulin aspart 30 (BIAsp 30) from human insulin (HI) was associated with improvement of glycaemic control. METHODS: A validated computer simulation model of diabetes was used to project long-term outcomes (such as quality-adjusted life expectancy and direct medical costs) based on patient characteristics and treatment effects observed in the Saudi Arabian PRESENT subgroup (n=598). Baseline prevalence of comorbidities was obtained from published sources. Primary research was performed in Riyadh and Jeddah to derive diabetes-related complication costs and patient management practices. RESULTS: Conversion to BIAsp 30 from HI was projected to increase life expectancy by 0.62 years (11.77 +/- 0.20 vs. 11.15 +/- 0.19 years) and quality-adjusted life expectancy by 0.96 quality-adjusted life years (QALYs) (7.03 +/- 0.12 vs. 6.07 +/- 0.11 QALYs). Direct medical cost savings of Saudi Arabian Riyals (SAR) 53,879 per patient were projected for conversion to BIAsp 30 therapy (SAR 84,761 +/- 3102 vs. SAR 138,640 +/- 4102 per patient). Cost savings were driven by lower costs of hypoglycaemia (SAR 286 vs. SAR 57,437 per patient), and lower costs of renal complications (SAR 18,848 vs. SAR 31,228) over patient lifetimes. CONCLUSION: Conversion to BIAsp 30 from HI was projected to improve life expectancy and quality-adjusted life expectancy while reducing lifetime direct medical costs.

Purulent constrictive pericarditis caused by Salmonella enteritidis in a patient with adult-onset Still's disease: A case report.

RATIONALE: Purulent pericarditis is a rare and usually fatal disease. Immunodeficiency state and preexisting pericardial effusion can predispose patients to infections. However, we are not aware of similar cases in patients with adult-onset Still's disease (AOSD). In addition, it is seldom caused by Salmonella bacteria. PATIENT CONCERNS: We report a 30-year-old woman with dyspnea on exertion and epigastric fullness. She was newly diagnosed with AOSD 4 months previously and medicated with prednisolone. DIAGNOSES: Transthoracic echocardiography (TTE) and computed tomography revealed a thickened pericardium with loculations in the pericardial space, consistent with purulent constrictive pericarditis. Subsequent cultures of blood and pericardial fluid yielded S enteritidis. INTERVENTIONS: She underwent subtotal pericardiectomy through a limited median sternotomy, and antibiotic therapy (ceftriaxone) for 1 month. OUTCOMES: The New York Heart Association functional classification downgraded from class III to class I. There was no recurrence during the 1-year follow-up. LESSONS: This case presents an opportunity to highlight the importance of considering purulent pericarditis in patients previously diagnosed with AOSD. High clinical suspicion, early diagnosis, and prompt management can result in a better outcome in purulent pericarditis.

Ectopic Thyroid Tissue in the Adrenal Gland Mimicking a Pheochromocytoma.

Ectopic thyroid tissue in the adrenal gland (ETTAG) usually presents as a well-circumscribed cystic mass on a CT scan. However, the MRI features of ETTAG are incompletely understood. We report a case of ectopic thyroid tissue in the adrenal gland, which demonstrates findings similar to those of a pheochromocytoma on the MRI.

Robotic totally endoscopic coronary artery bypass for isolated ostial stenosis of the left coronary artery.

Isolated ostial stenosis (IOS) is a rare disease that encroaches on aorto-coronary junction of uncertain etiology. All distal coronary vessels present normally. IOS occurs predominantly in premenopausal young women with few risk factors for atherosclerotic disease. Here, we report a 40-year-old woman who had experienced crescendo angina for 4 months. Surgical revascularization was achieved by robotic totally endoscopic coronary artery bypass (TECAB) with left internal thoracic artery (LITA) graft. She resumed her daily tasks without difficulties 1 week after the operation. Postoperative computed tomographic angiography disclosed good opacification of the LITA graft and distal runoff. Robotic TECAB is a potentially feasible alternative for IOS patients, particularly in premenopausal young woman, with obvious benefits of cosmetic appearance and speedy recovery.

Assessment with magnetic resonance imaging and spectroscopy in Lhermitte-Duclos disease.

Lhermitte-Duclos disease (LDD) is a rare benign lesion of uncertain pathogenesis characterized by distortion of the normal cerebellar laminar cytoarchitecture. We report a 22-year-old man admitted for injury sustained in a traffic accident with the incidental finding of a cerebellar mass. Magnetic resonance imaging (MRI) revealed a mass lesion within the right cerebellar hemisphere. The final diagnosis of LDD was made by obtaining a surgical specimen and identifying the characteristic appearance of the lesion by MRI study. The images showed the typical striated pattern of hyperintensity on T2-weighted images and corresponding hypointensity on T1-weighted images, as well as the typical absence of enhancement following gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) administration. In addition, no disturbance of water diffusion on diffusion-weighted MRI, and associations of decreases in the N-acetylaspartate/creatine (NAA/Cr) and NAA/Choline (Cho) ratios with near normal values of Cho/Cr, as well as an obvious lactate peak gave supplemental information for diagnosis.

Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Papanicolaou smears.

OBJECTIVE: To study clinical factors predicting the absence of endocervical/transformation zone (EC/TZ) components of conventional cervical Papanicolaou (Pap) smears. MATERIALS AND METHODS: The medical charts of patients who received Pap smears between March 2006 and August 2006 in the hospital were reviewed. The results of their Pap smears were retrieved while their demographic and clinical information were obtained from the medical charts. After excluding 378 cases with incomplete demographic data and 1397 cases with a history of pelvic irradiation, pelvic malignancy, and hysterectomy, 5662 cases were enrolled for data analysis. The relationship between clinical parameters and the absence of EC/TZ component was analyzed by Pearson Chi-square tests with Yates continuity correction and binary logistic regression tests. RESULTS: The incidence of satisfactory but absence of EC/TZ component was 8.7% (491/5662). Pregnancy increased the absence of EC/TZ component [odds ratio (OR}: 2.84, 95% confidence interval (CI): 2.14-3.77, p<0.0001]. Postpartum status and endocervical polyps decreased incidence (OR: 0.61, 95% CI: 0.38-0.98, p = 0.043 and OR: 0.33, 95% CI: 0.25-0.44, p<0.0001, respectively). CONCLUSIONS: Pregnancy is the only clinical factor associated with increased incidence of absence of EC/TZ cells. For these pregnant women undergoing a Pap smear, a more effective strategy may be needed to get a satisfactory smear with adequate EC/TZ components.

Colorectal mesenchymal tumor: a clinicopathologic study of 25 cases.

BACKGROUND: It is important to distinguish gastrointestinal stromal tumors (GISTs) from other gastrointestinal mesenchymal tumors (GIMTs), because of the malignant potential of GISTs and the availability of molecular targeted therapy. GISTs represent the most common subgroup of GIMTs, and rarely occur in the colon and rectum. The first objective of our retrospective study was to reclassify colorectal mesenchymal tumors, from files collected over 20 years, to determine if, based on immunohistologic features, the lesions were truly GISTs. The second objective was to identify the relationship between clinicopathologic features and prognostic factors of GISTs in the colon and rectum. METHODS: We evaluated all cases of colorectal mesenchymal tumor identified from the database of the Department of Surgical Pathology at Taichung Veterans General Hospital for the period 1983-2001. For 25 patients, clinical data, and information about tumor characteristics, surgical procedures, and survival outcomes, were obtained and analyzed. Histopathologic evaluations, and appropriate immunohistochemical markers, were used to distinguish between various GIMT subtypes. The relationship between KIT expression and clinicopathologic features was investigated. RESULTS: The following variables were significantly associated with different CD117 results: symptomatic presentation, location, gross features, tumor size, mitotic count, cellularity, and type of surgery. Only 18 tumors were identified as GISTs. For these, the following variables were significantly associated (by univariate analysis) with increased lethality: tumor size (p = 0.049); mitotic count (p = 0.019); nuclear atypia (p = 0.019); and tumor necrosis (p = 0.045). However, only mitotic activity showed a significant difference in the survival analysis (p = 0.0304; log-rank test). CONCLUSION: Two clinicopathologically different categories were identified from our colorectal mesenchymal tumors: intramural GISTs and polypoid submucosal leiomyomas. Our study suggests that GIST is a better categorization than smooth muscle tumor because of the malignant potential. Prognosis is strictly related to the number of mitoses. However, tumor size, nuclear atypia and tumor necrosis are probably also significant predictive factors of lethality. Future studies with DNA analysis and larger patient numbers are essential to evaluate the prognostic significance of our findings.

Ultraviolet/blue light-emitting diodes based on single horizontal ZnO microrod/GaN heterojunction.

We report electroluminescence (EL) from single horizontal ZnO microrod (MR) and p-GaN heterojunction light-emitting diodes under forward and reverse bias. EL spectra were composed of two blue emissions centered at 431 and 490 nm under forward biases, but were dominated by a ultraviolet (UV) emission located at 380 nm from n-ZnO MR under high reverse biases. Light-output-current characteristic of the UV emission reveals that the rate of radiative recombination is faster than that of the nonradiative recombination. Highly efficient ZnO excitonic recombination at reverse bias is caused by electrons tunneling from deep-level states near the n-ZnO/p-GaN interface to the conduction band in n-ZnO.

Malignant solitary fibrous tumor of the urinary bladder.

A 67-year-old man was examined for persistent pain over his lower abdomen and was found to have a large pelvic tumor. During surgery, we detected a 16 × 9 × 9 cm(3) urinary bladder tumor with small intestinal adhesions, and performed partial cystectomy and segmental resection. Histological and immunohistochemical examinations established the diagnosis of malignant solitary fibrous tumor (SFT). Only 10 cases of urinary bladder SFT have been reported in the English literature; our patient is the second one with malignancy and had a longer follow-up period than the other case.

Renal mucinous tubular and spindle cell carcinoma with an aorto-caval mass mimicking metastatic lymphadenopathy.

A 54-year-old female had a 9-cm left renal mass with a 12-cm aorto-caval mass lesion mimicking an enlarged lymph node. Retroperitoneal dissection and left radical nephrectomy were performed, and pathology revealed a left renal mucinous tubular and spindle cell carcinoma combined with a retroperitoneal ganglioneuroma. The patient has had no local recurrence or distant metastasis after 3 years' follow-up. A misdiagnosis of metastatic renal cell carcinoma may be upheld by the primary imaging studies. Even in the targeted therapy era, cytoreductive nephrectomy is still an important step in the diagnosis and treatment of suspicious metastatic renal cell carcinomas.

Invasive adenocarcinoma of the prostate with urethral tumor.

Metastases of prostate cancer to the penis and urethra are rare and often represent advanced disease. We describe a case of newly diagnosed prostatic adenocarcinoma with metastases to the corpus spongiosum, cavernosum, and the anterior urethra. A male patient, 77 years of age, initially had lower urinary tract obstruction symptoms. His prostate-specific antigen level was 5.02 ng/mL. Digital rectal examination disclosed stony hard tumors at both lobes of the prostate. Transrectal ultrasound-guided biopsy of the prostate revealed adenocarcinoma over both lobes; the Gleason score was 4 + 4 = 8. Cystoscopy showed a penile urethral tumor and biopsy disclosed metastatic adenocarcinoma of the prostate; the Gleason score was 4 + 4 = 8. The patient initially received hormone therapy. Biochemical failure developed after 15 months and rapidly progressed to a hormone-refractory stage. Docetaxel was then prescribed. The patient died in the 25(th) month after the diagnosis.