Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study.

A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.

RESNA position on the application of seat-elevating devices for wheelchair users.

This document, approved by the Rehabilitation Engineering & Assistive Technology Society of North America (RESNA) Board of Directors in September 2005, shares typical clinical applications and provides evidence from the literature supporting the use of seat-elevating devices for wheelchair

Synchronous and Metastatic Papillary and Follicular Thyroid Carcinomas with Unique Molecular Signatures.

Despite the relatively high prevalence of thyroid cancer, the occurrence of multiple synchronous, distinct subtypes of primary thyroid carcinoma is uncommon. The incidental finding of papillary thyroid microcarcinoma in a gland with a biologically relevant follicular or medullary carcinoma is more frequent than the synchronous occurrence of multiple clinically significant carcinomas. We report a case of synchronous papillary and follicular thyroid carcinomas metastatic to lymph node and bone, respectively. Next generation sequencing showed BRAF V600E mutation in the primary papillary carcinoma and NRAS Q61R mutation in the primary follicular carcinoma and bony metastasis. To our knowledge, this is the first reported case of synchronous and metastatic primary papillary and follicular carcinomas, and the first report of synchronous BRAF V600E mutated papillary and NRAS mutated follicular carcinoma.

Male Breast Carcinoma: A Clinical and Pathological Review.

Male breast carcinomas (MBCs) are rare neoplasms that account for 0.1% of all male cancers. Still, there are 2000 new cases of MCB diagnosed annually in the United States. Because of its rarity, data regarding the etiology, risk factors, diagnosis, management, and prognosis of MBC are limited. MBC shares some similarities with female breast carcinoma (FBC). This review will address the important clinical, histopathological, immunohistochemical and molecular features, genetics, management, and prognosis of MBC.

Myoepithelial carcinoma of the lung: a review.

Primary myoepithelial carcinoma of the lung is a rare neoplasm with only 8 cases reported in the English literature to date. Myoepithelial carcinomas of the lung are thought to arise from submucosal bronchial glands and have morphologic features similar to their salivary gland counterparts. The pathologic features and immunohistochemical profile of this tumor have not yet been summarized in the literature. Our objective is to review the clinicopathologic features and immunohistochemistry of these tumors.

Concurrent angiomyolipomas and renal cell neoplasms in patients without tuberous sclerosis: a retrospective study.

Synchronous renal cell neoplasms (RCNs) and angiomyolipomas (AML) occurring in the same kidney are rare. The aim of this retrospective study is to investigate the incidence and clinicopathological features of concurrent AML and RCN in patients without tuberous sclerosis complex (TSC). Partial and radical nephrectomy specimens with a diagnosis of RCN and AML from 1995 to May 2013 were reviewed. Cases were assessed for histological subtype of AML and RCN, topographic relationship between the AML and the RCN, and clinical characteristics. A total of 565 RCNs and 19 AMLs were identified. Of 19 cases of AML, 9 (47%) were associated with renal tumors. Clear-cell renal cell carcinoma (RCC) was the most common malignancy associated with AML (56%). The mean age of patients with concomitant AML and RCN was higher than the mean age of patients with only AML (58.6 vs 55.5 years). The majority of patients with concomitant AML and RCN were female (78%). All concurrent sporadic AMLs were benign. We identified one case of bilateral clear-cell RCC with concomitant multiple bilateral AMLs in a patient with TSC.

Myocardial hydrophilic polymer emboli following cardiac catheterization: a case report and literature review.

BACKGROUND: Intravascular polymer emboli have been reported in the skin, lungs, and brain following vascular procedures utilizing hydrophilic polymer coated devices. The Cook arterial introducer sheath was the first of these devices to be introduced, after which case reports followed documenting sterile inflammation at the sheath access site, characterized histologically by perivascular granulomas containing hydrophilic polymer. More recently, hydrophilic polymer emboli have been reported in the vessels of the lungs and brain in association with ischemia and infarct following vascular procedures using polymer coated devices. METHODS: We report a case of intravascular myocardial emboli associated with acute myocardial infarction following cardiac catheterization. The patient was a 65-year-old man who received cardiac catheterization with placement of a bare metal stent following myocardial infarction. One month later, the patient presented with angina and died shortly after admission. RESULTS: Autopsy revealed hemopericardium with rupture of the left ventricle through an aneurismal defect within the area of prior infarction. Microscopically, an area of acute infarction was present within the aneurismal defect. Numerous small and medium-sized vessels within the left ventricle were occluded by basophilic amorphous granular material with an inflammatory giant cell response. CONCLUSION: The emboli were most frequent in the area of acute infarction, suggesting that the emboli may have resulted in ischemia leading to the patient's death. This is the third documented case of intramyocardial polymer emboli following cardiac catheterization and the first case to our knowledge to document an association between intravascular myocardial polymer emboli and acute myocardial infarction.

Tandem parallel fragmentation of peptides for mass spectrometry.

Parallel fragmentations of peptides in the source region and in the collision cell of tandem mass spectrometers are sequentially combined to develop parallel collision-induced-dissociation mass spectrometry (p2CID MS). Compared to MS/MS spectra, the p2CID mass spectra show increased signal intensities (2-400-fold) and number of sequence ions. This improvement is attributed to the fact that p2CID MS virtually samples all the ions generated by electrospray ionization, including intact and fragment ions of different charge states from a peptide. We implement the method using a quadrupole time-of-flight tandem mass spectrometer. The instrument is operated in TOF-MS mode that allows the ions from source region broadband-passing the first mass analyzer to enter the collision cell. Cone voltage and collision energy are investigated to optimize the outcome of the two parallel CID processes. In the in-source parallel CID, elevated cone voltage produces singly charged intact peptide ions and large fragment ions, as well as decreases the charge-state distribution of peptide ions mainly to double and single charges. The in-collision-cell parallel CID is optimized to dissociate the ions from the source region to produce small and medium fragment ions. The method of p2CID MS is especially useful for sequencing of large peptides with labile amide bonds and peptides with C-terminal arginine. It has unique potential for de novo sequencing of peptides and proteome analysis, especially for affinity-enriched subproteomes.