Citations

PurposeTo develop a reconstruction pipeline that intrinsically accounts for both simultaneous multislice echo planar imaging (SMS‐EPI) reconstruction and dynamic slice‐specific Nyquist ghosting correction in time‐series data.MethodsAfter 1D slice‐group average phase correction, the separate polarity (i.e., even and odd echoes) SMS‐EPI data were unaliased by slice GeneRalized Autocalibrating Partial Parallel Acquisition. Both the slice‐unaliased even and odd echoes were jointly reconstructed using a model‐based framework, extended for SMS‐EPI reconstruction that estimates a 2D self‐phase map, corrects dynamic slice‐specific phase errors, and combines data from all coils and echoes to obtain the final images.ResultsThe percentage ghost‐to‐signal ratios (%GSRs) and its temporal variations for MB3Ry2 with a field of view/4 shift in a human brain obtained by the proposed dynamic 2D and standard 1D phase corrections were 1.37 ± 0.11 and 2.66 ± 0.16, respectively. Even with a large regularization parameter λ applied in the proposed reconstruction, the smoothing effect in fMRI activation maps was comparable to a very small Gaussian kernel size 1 × 1 × 1 mm3.ConclusionThe proposed reconstruction pipeline reduced slice‐specific phase errors in SMS‐EPI, resulting in reduction of GSR. It is applicable for functional MRI studies because the smoothing effect caused by the regularization parameter selection can be minimal in a blood‐oxygen‐level–dependent activation map.

Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC), originally known as HPV-related carcinoma with adenoid cystic carcinoma-like features, is a peculiar neoplasm that is restricted to the sinonasal tract, exhibits features of both a surface-derived and salivary gland carcinoma (particularly adenoid cystic carcinoma), and is associated with high-risk HPV. Given the limited number of published cases, the full clinicopathologic spectrum of this neoplasm is unclear. Here, we present an updated experience of 49 cases. All cases of HMSC were obtained from the authors’ files. Immunohistochemistry for p16, c-kit, and myoepithelial cell markers (S100, actin, calponin, p63, and/or p40) was performed along with RNA in situ hybridization for HPV (type 33-specific as well as a high-risk cocktail). Fluorescence in situ hybridization studies for fusions ofMYB,NFIB, andMYBL1was performed on a subset of cases. Clinical follow-up was obtained from medical records. A total of 49 cases of HMSC were collected. Twenty-eight (57%) were from women and 18 (43%) from men, ranging in age from 28 to 90 years (mean, 54 y). Of 40 cases with detailed staging information, 43% of HMSCs presented with a high T-stage (T3 or T4). Histologically, most grew predominantly as solid nests of basaloid cells exhibiting high mitotic rates and frequent necrosis, with histologic and immunohistochemical evidence of myoepithelial differentiation. Most cases also demonstrated foci of cribriform and/or tubular growth, along with an inconspicuous population of ducts. Thirty-four (69%) cases demonstrated an unusual pattern of surface involvement where markedly atypical squamous cells colonized tracts of the sinonasal mucosa. Less consistent histologic features included squamous differentiation within the invasive tumor (n=6), sarcomatoid transformation (n=5) including overt chondroid differentiation (n=3), and prominent epithelial-myoepithelial carcinoma-like growth (n=3). All cases were positive for p16 by immunostaining and HPV by RNA in situ hybridization. Thirty-three (67%) were positive for HPV 33. No cases tested forMYB,MYBL1, orNFIBgene fusions were positive. In the 38 cases with follow-up data, (mean follow-up, 42 mo) 14 recurred locally and 2 metastasized (lung, finger). There were no regional lymph node metastases, and no tumor-related deaths. HMSC is a distinct sinonasal neoplasm characterized by myoepithelial differentiation, frequent surface epithelial involvement, and the presence of high-risk HPV (especially type 33). Although it classically exhibits a cribriforming pattern that closely resembles adenoid cystic carcinoma, our expanded series highlights a histologic spectrum that is much broader than previously recognized, warranting a change in terminology. HMSC usually presents as a large and destructive sinonasal mass with high-grade histologic features, but it paradoxically behaves in a relatively indolent manner, underscoring the importance of distinguishing HMSC from true adenoid cystic carcinoma, squamous cell carcinoma, and other histologic mimickers.

Abstract Lung cancer is the most lethal malignancy around the world. In Hong Kong, chronic tobacco use is prevalent in male but <20% of female patients smoke. Epidermal growth factor receptor (EGFR) mutations affect 30% and 67% of male and female lung adenocarcinomas, respectively. Treatment responses to tyrosine kinase inhibitors (TKI) are not uniform and all patients eventually develop drug resistance. Mutation screening of immediate pre-treatment tumors is the most ideal for assessing drug targets but in practice, excision specimens of primary or metastatic sites are more efficient in terms of tumor quantity, timeliness and patient acceptance. However, information on the applicability of this approach and correlation with the clinical outcome is limited. For this purpose, we compared the whole exome mutation profiles of 39 excised EGFR mutant cancers treated with first line TKI with the clinical response type, including 15 stage I/II and 24 stage III/IV tumors. They included 16 non-responders (NR) defined clinically as those with stable or progressive disease, and 23 responders (R) defined by partial or complete tumor shrinkage. Considering only the non-synonymous SNV and INDEL mutations of coding regions of known actionable targets and genes listed in both the CGC and COSMIC cancer databases, the tumors harbored 54 mutated genes including 26 recurrently mutated and 28 genes involving only 1 tumor. Excluding EGFR, TP53 was the most commonly mutated gene occurring in 25/39 (64.1%) cases. Most known resistant genes involved in the EGFR and bypass signaling network showed mutations only in the NR group including recurrent mutations of PTEN (3/16), PIK3CA (2/16) and NF1 (2/16), and single case mutations of AKT1, ALK, RAF1 and KDR. Two EGFR network candidates showed mutations in both the NR and R groups, including HGF (2/16 NR, 1/23 R) and ROS1 (1 case in either group). Four post-treatment (post-TKI) tumors of acquired resistance were also analyzed, all of which showed EGFR T790M while no pre-treatment NR or R tumor harbored this mutation. Notably, mutations in the β-catenin pathway were prominent in the NR and post-TKI tumors, including APC (2/16 NR), CTNNB1 (1/16 NR, 1/4 post-TKI) and c-MYC (1/16 NR, 1/4 post-TKI) while they were not detected in the R tumors. Also, nonsense mutations of ARID1A was observed in 2/16 NR but none of the R tumors. In summary, our findings revealed candidate TKI resistant mutations involving the EGFR and bypass signaling networks in pre-treatment excision specimens particularly in non-responding patients. The EGFR T790M was not detectable in pre-treatment samples but was prevalent in post-TKI treated cancers. While this study is limited by its small cohort size, the findings indicate deep sequencing analysis of pre-treatment excision specimens of EGFR-mutant lung adenocarcinomas is warranted for detection of resistant mutations and predicting treatment response. Note: This abstract was not presented at the meeting. Citation Format: Xu-yuan Gao, Hang Xu, James CM Ho, Oscar SH Chan, Feng Xu, Junwen Wang, Victor HF Lee, Vicky PC Tin, Zhijie Xiao, Siqi Wang, Judy WP Yam, Maria P. Wong. Whole-exome sequencing reveals tyrosine kinase-resistant mutations in pretreatment EGFR-mutant lung adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-274. doi:10.1158/1538-7445.AM2017-LB-274

AbstractBased on cytoarchitecture, the posterior cingulate cortex (PCC) is thought to be comprised of two distinct functional subregions: the dorsal and ventral PCC (dPCC and vPCC). However, functional subregions do not completely match anatomical boundaries in the human brain. To understand the relationship between the functional organization of regions and anatomical features, it is necessary to apply parcellation algorithms based on functional properties. We therefore defined functionally informed subregions in the human PCC by parcellation of regions with similar patterns of functional connectivity in the resting brain. We used various patterns of functional connectivity, namely local, whole‐brain and diffuse functional connections of the PCC, and various clustering methods, namely hierarchical, spectral, andk‐means clustering to investigate the subregions of the PCC. Overall, the approximate anatomical boundaries and predicted functional regions were highly overlapped to each other. Using hierarchical clustering, the PCC could be clearly separated into two anatomical subregions, namely the dPCC and vPCC, and further divided into four subregions segregated by local functional connectivity patterns. We show that the PCC could be separated into two (dPCC and vPCC) or four subregions based on local functional connections and hierarchical clustering, and that subregions of PCC display differential global functional connectivity, particularly along the dorsal‐ventral axis. These results suggest that differences in functional connectivity between dPCC and vPCC may be due to differences in local connectivity between these functionally hierarchical subregions of the PCC.Hum Brain Mapp 38:2808–2818, 2017. ©2017 Wiley Periodicals, Inc.

We have produced an antiserum to porcine parathyroid hormone (PTH) which distinguishes between the PTH in human hyperparathyroid serum and that in extracts of parathyroid adenomata. The PTH secreted into the medium by parathyroid adenoma slices in culture reacts with this antiserum in the same way as the PTH in human hyperparathyroid serum, but extraction of the same serum by a conventional procedure used for the extraction of glandular tissue converts the serum hormone to a species which reacts more like hormone extracted from adenomata. The results suggest that we have immunologically identified a native molecular species of PTH, that the antiserum used recognizes primarily this species in human hyperparathyroid serum, and that the PTH extracted from parathyroid adenomata is immuno-chemically altered.