Small Cell Tumor Research Articles

Systemic Therapy for Small Cell Lung Cancer

Small cell lung cancer is an aggressive tumor characterized by genetic complexity, rapid doubling time, and early development of disseminated disease. Unfortunately, few chemotherapeutic advances have been made in the treatment of extensive-stage disease, and cisplatin/etoposide has remained the standard of care for more than 30 years. Other regimens with comparable efficacy include cisplatin/irinotecan and carboplatin/etoposide. Each of these combinations is associated with a different toxicity profile that must be considered when selecting an initial regimen. Several strategies, including maintenance chemotherapy, 3-drug combinations, alternating combination chemotherapy regimens, and high-dose chemotherapy, have consistently failed to demonstrate improvements in survival when compared with 4 to 6 cycles of platinum doublets. Several options are available for patients who experience progression during or relapse after induction therapy, although topotecan is the only FDA-approved agent for second-line treatment. Recently, scientific efforts have identified potentially actionable genetic alterations in small cell tumors that may lead to the development of effective, targeted therapies.

Microcavity Array System for Size-Based Enrichment of Circulating Tumor Cells from the Blood of Patients with Small-Cell Lung Cancer

In this study, we present a method for efficient enrichment of small-sized circulating tumor cells (CTCs) such as those found in the blood of small-cell lung cancer (SCLC) patients using a microcavity array (MCA) system. To enrich CTCs from whole blood, a microfabricated nickel filter with a rectangular MCA (10(4) cavities/filter) was integrated with a miniaturized device, allowing for the isolation of tumor cells based on differences in size and deformability between tumor and blood cells. The shape and porosity of the MCA were optimized to efficiently capture small tumor cells on the microcavities under low flow resistance conditions, while allowing other blood cells to effectively pass through. Under optimized conditions, approximately 80% of SCLC (NCI-H69 and NCI-H82) cells spiked in 1 mL of whole blood were successfully recovered. In clinical samples, CTCs were detectable in 16 of 16 SCLC patients. In addition, the number of leukocytes captured on the rectangular MCA was significantly lower than that on the circular MCA (p < 0.001), suggesting that the use of the rectangular MCA diminishes a considerable number of carryover leukocytes. Therefore, our system has potential as a tool for the detection of CTCs in small cell-type tumors and detailed molecular analyses of CTCs.

The Small Round Blue Cell Tumors of the Sinonasal Area: Histological and Immunohistochemical Findings

BackgroundPrimary Small round blue cell tumors (SRBCT) in sinonasal comprise histogenetically diverse entities with overlapping morphologic features. Because of the limited initial biopsy tissue materials, differential diagnostic difficulties may arise, and as they have different management, exact diagnosis and classification are very important.ObjectivesIn this study, we analyzed the immunohistochemical expression of a panel of markers in the classification and diagnosis of sinonasal SRBCTs.Material and MethodsThis cross sectional study was performed on 36 paraffin embedded tissue samples. Histologic and immunohistochemical slides from 36 patients with SRBCT were analyzed retrospectively. The patients were admitted in Khalili hospital, Shiraz from 1383 to 1388.ResultsThere were 13 women and 23 men with the mean age of 53 ±12.1. There were 9 malignant melanoma, seven poorly differentiated SCC; six lymphoma (DLBL); 4 SCNEC; three SNUC; two ON; two Ewing/PNET; two embryonal rhabdomyosarcoma, and one plasmacytoma. Pan-cytokeratin was strongly expressed poorly differentiated SCC and all cases of SNUC. Coexpression of desmin and nuclear myoD1 was only detected in rhabdomyosarcoma. HMB45 was only expressed in sinonasal melanoma. CD99 expression was identified only in Ewing/PNET. FLI-1 was detected in 50% of PNET. P63 was expressed in poorly differentiated SCC (2/7) and SNUC (1/3).ConclusionsThe results of our study indicate that the integration of histopathologic findings with application of limited but highly specific markers led to the separation of carcinomas, lymphoma and melanomas from other small cell tumors. Using a panel of keratin, LCA, desmin, and HMB45 is the most practical and economic approach to accurately classify these tumors.

PTH-189 Double Balloon Enteroscopy in the Elderly with Obscure GI Bleeding- is it Worth the Push and Pull?

IntroductionDouble Balloon enteroscopy (DBE) is an increasingly important procedure particularly in the context of obscure GI bleeding (OGB) with a high reported diagnostic yield. There is however paucity of data...

Deepening on Breast Cancer Metastasis: The ERα-Mediated Modulation of KISS/KISS1R System

Breast cancer is one of the most important diseases worldwide with an annual global fatality of almost 800 000 and the primary cause of cancer mortality in women (1). The risk of breast cancer is age dependent. The probability of developing breast cancer is equal to 0.04% per year for average risk women between age 30 and 39 and increases to more than 10% per year in those over 80 years (2). Breast cancer in women under 40 years is not a common condition. However, a dramatic increase in the number of breast cancers diagnosed in premenopausal women has been reported in several countries. In the United States, 5.5% of breast cancers occur in women younger than the age of 40 years. Approximately 1 in 40 women diagnosed with early breast cancer is very young ( 35 y). Breast cancer in young women is associated with a positive family history and gene mutations more frequently than in older women (3). However, the mainly cause of deaths is not the primary tumors itself but also the result of metastasis to others organs (4). The biological mechanisms of metastasis development have been studied for more than 100 years. However, knowledge of all the cellular and molecular mechanisms that trigger it is still unclear. Further research is necessary to better understand this process, discover solutions for its prevention, and provide patients with a longer life expectancy. The steps involved in the process of metastasis are often described as the “metastatic cascade,” where single tumor cells or small tumor cell aggregates first detach and leave the primary tumor; next, the cells infiltrate the surrounding stroma (invasion) and enter into the circulatory system (intravasation); and finally, they travel to distinct sites where they establish secondary tumor growth (extravasation) (5–9). This seemingly simple process is one of the main concerns of current biomedical science, so when an interesting finding providing hope is encountered, nature itself appears to be illustrating its inherent complexity. In this difficult path toward understanding this complex process, Cvetkovic et al (10) have opened a new door that will give rise to new research in the near future. They have focused their research in Kisspeptin receptor (KISS1R), also known as GPR54. This is a G protein-coupled receptor that binds kisspeptins (Kps). Kps are neuropeptides encoded by KISS1 and are the natural ligands of the KISS1R. These were initially described as metastasis inhibitors in melanoma (11). Later it was demonstrated that loss-of-function mutations in KISS1R cause absence of puberty and low LH and FSH levels in humans (12, 13). Therefore, the major role for the KISS/KISS1R system is to regulate the gonadotropic axis at puberty and during adulthood via tight modulation of GnRH secretion (14). KISS/KISS1R is also expressed outside of central nervous system and seems to play a pivotal role in metastatic pathways. Loss of KISS1 expression has also been correlated with increased metastasis and/or cancer progression in malignant pheochromocytoma (15), esophageal squamous cell carcinoma (16), bladder (17), ovarian (18), gastric (19), and pancreatic (20) tumors. Moreover, specific animal studies examining KISS1 in breast cancer clearly demonstrated suppression of metastases in vivo (11, 18, 21, 22). In contrast, Martin et al (23) found KISS1 messenger elevated in node-positive breast tumors in comparison with node-negative samples, yet no differences were observed in KISS1R, and other authors indicate that KISS1R signaling may correlate positively with breast tumor progression and metastatic potential (24, 25). A possible explanation for this paradox could be the associations of Kps

Triggers in the pathway from lung cell damage to malignancy: The glycans.

e22189 Background: It has been reported that carbon nanoparticles (CN) produce mesothelioma as readily as do asbestos fibers. We have studied early CN damage in experimental animals, quantifying toxicity by release from cells of the nuclear chaperone HMGB1. Damage-released HMGB1 binds to receptors (RAGE, CD24) to upregulate cytokines and produce regulatory signals that control cell homeostasis. Further, HMGB1 has recently been shown to form a complex with P53, one of the most commonly mutated genes in human cancers, and HMGB1 is the controlling factor in autophagy, an important new field in translational cancer research. Methods: One HMGB1 receptor, CD24, is the source of a whole-receptor antibody used to determine extent of malignancy during surgery. CD24 is highly glycosylated. We hypothesized that carbohydrate vs protein specificity would show differences in tumor character. Would antibodies to the CD24 carbohydrate moiety reflect a tumor glycan character, and how would this relate to the tumor profile such as metastasis? With cooperation of TMC pathology Dept, blocks (N=15 each) of lung squamous cell, adenocarcinoma, and small cell cancer were sectioned and stained with mouse monoclonals to CD24, IgM –glycan, IgG-protein fraction. Results: Small cell and adenocarcinoma lung tumors showed mostly similar staining by CD24 protein vs CD24 glycan antibodies. Squamous cell CA showed elevated carbohydrate CD24 staining with negative or low protein stain in over half of the cases, and examination of patient records are being studied to determine metastatic character, lung- damage history and tumor chemotherapy response. Conclusions: Squamous cell tumors demonstrate significantly more staining by antibody to the glycan moiety of CD24, p=0.02. There was no relationship between numbers of positive nodes and staining, although other chart information awaits analysis. Research continues into the significance of this glycan CD24 receptor for HMGB1, our marker for nanoparticle lung damage, and its relationship to malignant transformation. [Table: see text]

First-in-human trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors.

2580 Background: BMN 673 is the most potent and specific inhibitor of PARP1/2 in clinical development (IC50&lt;1nM). In tumors genetically dependent on DNA repair by homologous recombination PARP inhibition induces synthetic lethality. Methods: Pharmacokinetics (PK), pharmacodynamics (PD), safety and anti-tumor activity of BMN 673 were evaluated in a 2-stage dose-escalation study with 3-6 patients (pts)/dose level. In dose escalation (Stage 1) cycle 1 was 6 wks, with drug taken on days 1 and 8-35, for PK and PD assays, followed by daily continuous dosing in 4-wk cycles. Stage 2 (expansion at MTD) recruits pts with tumors defective in DNA repair: Ewing sarcoma, small cell lung cancer or tumors associated with BRCA mutation (mut). Results: 39 pts (33F/6M) were enrolled in 9 cohorts from 25 to 1100 µg/d that defined a MTD of 1000 µg/d. Median (range) age was 58 (19-81), PS 0 (0-1) and # of prior therapies 4 (1-13). Tumors (# with deleterious BRCA 1/2 mut) included 23 ovarian/primary peritoneal (17); 8 breast (6); 3 pancreas; 2 colon; 1 prostate (1), and 1 mullerian carcinosarcoma. 17 and 8 pts had BRCA 1 and 2 mut, respectively. Dose-limiting thrombocytopenia occurred in 1/6 and 2/5 pts at 900 and 1100 µg/d, respectively. Potentially-related adverse events in &gt;10% of pts (# grade 1 and 2/grade 3 and 4) included fatigue (10/0); nausea (10/0); flatulence (4/0); anemia (5/2); neutropenia (4/3); thrombocytopenia (1/3); and grade 1 alopecia (10). Inhibition of PARP activity in PBMCs was observed at doses ≥ 100 µg/d. BMN 673 plasma concentrations peaked 1-2 hrs post-dose; exposure increased dose proportionally. Steady state plasma concentrations were reached by the end of the 2nd week of daily dosing; mean Cmax: 0.30 - 25.4 ng/mL and AUC0-24: 3.96 - 203 ng-hr/mL across the 25 to 1100 µg/d dose range after 28d of daily dosing. RECIST and/or CA-125 responses occurred at doses ≥ 100 µg/d in 11/17 BRCA carrier ovarian/peritoneal cancer pts. Objective responses occurred in 2/6 BRCA-carrier breast cancer pts. Conclusions: BMN 673 is well tolerated with impressive anti-tumor activity in pts with BRCA mut with a single agent recommended Phase II trial dose of 1000 µg/d due to dose-limiting thrombocytopenia. Clinical trial information: NCT01286987.

Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors

Well-differentiated small intestinal neuroendocrine tumors are rare malignancies. They arise from enterochromaffin cells and very little is known about differential microRNA (miRNA) expression. The aim of this study was to identify the miRNA profile of well-differentiated small intestinal neuroendocrine tumors, which may have a critical role in tumor development, progression and potentially develop miRNAs as novel clinical biomarkers. Specimens from two test groups, 24 small intestinal neuroendocrine tumor specimens at different stages of malignancy, are included in this study. Total RNA from the first test group, five primary tumors, five mesentery metastases and five liver metastases was hybridized onto the Affymetrix Genechip miRNA arrays to perform a genome-wide profile. The results were validated by using quantitative real-time PCR (QRT-PCR) and northern blot analyses. We then expanded the investigation to laser capture microdissected small intestinal neuroendocrine tumor cells and immuno-laser capture microdissected normal enterochromaffin cells of the first test group. Furthermore, a second test group, three primary tumors, three mesentery metastases and three liver metastases, was included in the study. Thus, two independent test groups validated the data by QRT-PCR. Moreover, we characterized nine miRNAs, five (miR-96, -182, -183, -196a and -200a), which are upregulated during tumor progression, whereas four (miR-31, -129-5p, -133a and -215) are downregulated. Several online software programs were used to predict potential miRNA target genes to map a number of putative target genes for the aberrantly regulated miRNAs, through an advanced and novel bioinformatics analysis. Our findings provide information about pivotal miRNAs, which may lead to further insights into tumorigenesis, progression mechanisms and novel therapeutic targets recognition.

Abstract 1458: Efficient isolation of circulating tumor cells in small cell lung cancer patients using size- and geometry-controlled microcavity array system.

Abstract Background: We have developed a microcavity array (MCA) system integrated with a miniaturized device for the isolation of circulating tumor cells (CTC) without relying on EpCAM expression. The MCA system allows the filtration of tumor cells from whole blood on the basis of differences in the size between tumor and blood cells. The previous study has shown that the MCA system is potentially superior to the conventional epithelial antigen-based method for detecting CTCs in non-small cell lung cancer. Recently, we further optimized the shape and porosity of MCA to efficiently isolate smaller tumor cells as in small cell lung cancer (SCLC). Here we report the results of clinical study in SCLC patients comparing MCA system to CellSearch system and exploratory study of novel rectangular-shaped MCA system. Methods: The MCA is made of nickel by electroforming and circular MCA is fabricated with 8-9 μm diameter pores. Meanwhile, novel rectangular-shaped MCA is fabricated with 5-9 μm-wide and 30-60 μm-long pores. NCI-H69 (12 μm in diameter) SCLC cells were used for spike-in experiments. CTCs were defined as cells with round to oval morphology, a visible nucleus, positive for cytokeratin and negative for CD45. For the clinical evaluation, paired peripheral blood samples were collected from 18 SCLC patients to compare the performance of the CellSearch system and the MCA system for CTC detection. Results: The recovery rate of spiked NCI-H69 cells with the rectangular-shaped MCA (80 ± 2%) was significantly higher than that with the circular MCA (67 ± 4%) (p=0.01, t-test). In addition, the carryover of leukocytes on the rectangular-shaped MCA was 7-fold lower than that on the circular MCA in the experiment using healthy donor blood. The fluctuation of flow resistance during filtration with the rectangular-shaped MCA (&amp;lt;1.5 kPa) was smaller than that with the circular MCA (2 kPa); the rectangular-shaped MCA enabled recovery of small tumor cells with high efficiency. In clinical study, compared to the CellSearch, the circular and rectangular-shaped MCA system identified significantly more SCLC patients (9 of 18 vs. 18 of 18 vs. 17 of 18, respectively) as CTC positive. No significant difference was observed in the CTC counts between the rectangular-shaped MCA (median 16, range 0-545 cells/7.5 mL) and the circular MCA (median 23, range 2-2329 cells/7.5 mL) (p=0.77, Wilcoxon test). In contrast, the number of captured leukocytes on the rectangular-shaped MCA was significantly lower than that on the circular MCA (p&amp;lt;0.0001, Wilcoxon test), suggesting that implementing the rectangular-shaped MCA diminishes a considerable number of carryover leukocytes. Conclusion: The MCA system has a potential as a tool for the efficient recovery of CTCs in small cell type tumors with high purity, while offering the additional advantages in cost, portability, and capacity to perform more detailed analyses of CTCs. Citation Format: Masahito Hosokawa, Hirotsugu Kenmotsu, Yasuhiro Koh, Tomoko Yoshino, Tsuyoshi Tanaka, Tateaki Naito, Toshiaki Takahashi, Haruyasu Murakami, Yukiko Nakamura, Asuka Tsuya, Takehito Shukuya, Akira Ono, Hiroaki Akamatsu, Reiko Watanabe, Sachiyo Ono, Hisashige Kanbara, Tadashi Matsunaga, Nobuyuki Yamamoto. Efficient isolation of circulating tumor cells in small cell lung cancer patients using size- and geometry-controlled microcavity array system. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1458. doi:10.1158/1538-7445.AM2013-1458

Askin’s Tumor - A Rare Case Report and Literature Review

Askin’s Tumour (Synonym: Primitive Neuro-Ectodermal Tumor) is a rare neoplasm of the chest wall. In 1979 Askin and Rosai described an unique clinicopathological entity, characterised as a malignant small-cell tumour of the soft tissues of the chest wall in childhood and adolescence. We report on a case of a 30-year old male who had a massive tumour in the left thorax. The clinical symptoms were cough and increasing dyspnoea. The tumour was revealed as a Primitive Neuro-Ectodermal Tumor (PNET) compatible with ASKIN’s Tumor by CT-guided fine needle aspiration. Immunohistochemical studies showed positive staining for CD99. In our case , radiotherapy followed by chemotherapy was given. Microscopy and immunohistological stain of the specific marker—neuron-specific enolase—are essential. Multimodal treatment allows a long-term survival, but often the prognosis is variable.DOI: http://dx.doi.org/10.3329/jom.v14i1.14588 J MEDICINE 2013; 14 : 94-97

Radioimmunotherapy for Peritoneal Cancers

Peritoneal carcinomatosis is the most common secondary cancerous disease to affect the peritoneal cavity, implying poor prognosis. Standard therapy consists of cytoreductive surgery in combination with adjuvant chemotherapy. To improve the therapeutic outcome, targeted therapy using radionuclides such as α-, β- and Auger emitters coupled to antibodies seems a promising option. Although β-emitters have shown promising results in preclinical and clinical Phase I/II studies, these results could not be confirmed in Phase III studies. Because α-particles very efficiently eradicate small tumor cell nodules, they represent a promising option for treatment of micrometastatic disease characteristic of peritoneal carcinomatosis. α-emitter radioimmunoconjugates have been successfully used in various experimental studies and in a first clinical Phase I study in human ovarian cancer. Although confirmation of these results in clinical trials is missing and problems still exist concerning worldwide availability, α-emitters could contribute to optimizing strategies for therapy of peritoneal carcinomatosis.

Christia vespertilionis plant extracts as novel antiproliferative agent against human neuroendocrine tumor cells

Neuroendocrine tumors respond poorly to radiation and conventional chemotherapy, hence surgical removal of the neoplastic tissue is still the most effective way of treatment. In an attempt to find new therapeutic plant extracts of Christia vespertilionis (CV) their antitumor potential in human medullary thyroid carcinoma (MTC) and human small intestinal neuroendocrine tumor (SI-NET) cell lines were tested. Proliferation and viability were analyzed using cell counting and WST-1 assay. Apoptosis was determined by microscopy, luminescence assays for caspases 3/7, and expression studies of apoptosis-related genes. CV extracts showed antiproliferative and proapoptotic effects in all MTC and SI-NET cell lines, whereby high growth inhibition was observed by treatment with the ethylacetate-extracts (CV-45) in tumor cell lines but not in normal human fibroblasts. Furthermore CV-45 treatment resulted in alterations of gene expression of PDCD5, MTDH and TNFRSF10b in MTC as well as in SI-NET cells. The results indicate that Christia vespertilionis could serve as an anticancer therapeutic for treatment of neuroendocrine tumors.

Reproducibility of Dynamic Contrast-enhanced MR Imaging: Why We Should Care

HomeRadiologyVol. 266, No. 3 PreviousNext Reviews and CommentaryEditorialsReproducibility of Dynamic Contrast-enhanced MR Imaging: Why We Should CareVicky Goh , Tobias Schaeffter, Martin LeachVicky Goh , Tobias Schaeffter, Martin LeachAuthor AffiliationsFrom the Division of Imaging Sciences and Biomedical Engineering, King’s College London, Imaging 2, Level 1, Lambeth Wing, St Thomas’s Hospital, Lambeth Palace Rd, London SE1 7EH, England (V.G., T.S.); Department of Radiology, Guy’s and St Thomas’ NHS Foundation Trust, London, England (V.G.); and Cancer Research UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, England (M.L.).Address correspondence to V.G. (e-mail: [email protected]).Vicky Goh Tobias SchaeffterMartin LeachPublished Online:Mar 1 2013https://doi.org/10.1148/radiol.12122447MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractThe results of two studies published in this issue of Radiology stress the difficulties of performing dynamic contrast-enhanced MR imaging across different commercially available software platforms in clinical practice, but more important suggest a potential solution.References1 Messiou C, Orton M, Ang JEet al.. Advanced solid tumors treated with cediranib: comparison of dynamic contrast-enhanced MR imaging and CT as markers of vascular activity. Radiology 2012;265(2):426–436. Link, Google Scholar2 Nathan P, Zweifel M, Padhani ARet al.. Phase I trial of combretastatin A4 phosphate (CA4P) in combination with bevacizumab in patients with advanced cancer. Clin Cancer Res 2012;18(12):3428–3439. Crossref, Medline, Google Scholar3 Leach MO, Brindle KM, Evelhoch JLet al.. The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations. Br J Cancer 2005;92(9):1599–1610. Crossref, Medline, Google Scholar4 Leach MO, Morgan B, Tofts PSet al.. Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging. Eur Radiol 2012;22(7):1451–1464. Crossref, Medline, Google Scholar5 Quantitative Imaging Biomarkers Alliance. Profile: DCE MRI Quantification Version 1.6. Quantitative Imaging Biomarkers Alliance [serial online]. http://qibawiki.rsna.org/images/7/7b/DCEMRIProfile_v1_6-20111213.pdf. Published 2011. Accessed December 19, 2012. Google Scholar6 Heye T, Davenport MS, Horvath JJet al.. Reproducibility of dynamic contrast-enhanced MR imaging. I. Perfusion characteristics in the female pelvis by using multiple computer-aided diagnosis perfusion analysis solutions. Radiology 2013;266(3):801–811. Link, Google Scholar7 Heye T, Merkle EM, Reiner CSet al.. Reproducibility of dynamic contrast-enhanced MR imaging. II. Comparison of intra- and interobserver variability with manual region of interest placement versus semiautomatic lesion segmentation and histogram analysis. Radiology 2013;266(3):812–821. Link, Google Scholar8 Goh V, Halligan S, Bartram CI. Quantitative tumor perfusion assessment with multidetector CT: are measurements from two commercial software packages interchangeable? Radiology 2007;242(3):777–782. Link, Google Scholar9 Goh V, Halligan S, Gharpuray A, Wellsted D, Sundin J, Bartram CI. Quantitative assessment of colorectal cancer tumor vascular parameters by using perfusion CT: influence of tumor region of interest. Radiology 2008;247(3):726–732. Link, Google Scholar10 Miles KA, Lee TY, Goh Vet al.. Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography. Eur Radiol 2012;22(7):1430–1441. Crossref, Medline, Google ScholarArticle HistoryReceived November 1, 2012; revision requested November 3; final revision received and accepted November 19.Published online: Mar 2013Published in print: Mar 2013 FiguresReferencesRelatedDetailsCited ByBritish Journal of Cancer, Vol. 125, No. 5Interreader Variability of Dynamic Contrast-enhanced MRI of Recurrent Glioblastoma: The Multicenter ACRIN 6677/RTOG 0625 StudyDaniel P. Barboriak, Zheng Zhang, Pratikkumar Desai, Bradley S. Snyder, Yair Safriel, Robert C. McKinstry, Felix Bokstein, Gregory Sorensen, Mark R. Gilbert, Jerrold L. Boxerman, 27 November 2018 | Radiology, Vol. 290, No. 2BMC Bioinformatics, Vol. 20, No. 1The British Journal of Radiology, Vol. 92, No. 1096European Radiology, Vol. 28, No. 9European Radiology, Vol. 27, No. 12La radiologia medica, Vol. 122, No. 4Lung Cancer, Vol. 93BMC Medical Imaging, Vol. 16, No. 1Journal of Magnetic Resonance Imaging, Vol. 42, No. 5Echocardiography, Vol. 32, No. 8Magnetic Resonance Imaging, Vol. 32, No. 3Recommended Articles Spontaneous Pregnancy with a Live Birth after Conventional and Partial Uterine Fibroid EmbolizationRadiology2017Volume: 285Issue: 1pp. 302-310The Blood–Cerebrospinal Fluid Barrier May Play a Role in Alzheimer Disease PathogenesisRadiology2022Volume: 304Issue: 3pp. 646-647Subfertility: What the Radiologist Needs to KnowRadioGraphics2017Volume: 37Issue: 5pp. 1587-1602Monitoring Neoadjuvant Chemotherapy for Breast Cancer by Using Three-dimensional Subharmonic Aided Pressure Estimation and Imaging with US Contrast Agents: Preliminary ExperienceRadiology2017Volume: 285Issue: 1pp. 53-624D Contrast-enhanced MR Angiography with the Keyhole Technique in Children: Technique and Clinical ApplicationsRadioGraphics2016Volume: 36Issue: 2pp. 523-537See More RSNA Education Exhibits Uterine Fibroid Embolization: Preparing for and Treating Post-Procedure PainDigital Posters2018Clinical Factors Related to Technical Success of Magnetic Resonance-Guided High-Intensity Focused Ultrasound Treatment of Uterine FibroidDigital Posters2020Oncologic Magnetic Resonance ElastographyDigital Posters2020 RSNA Case Collection Recurrent small bowel leiomyosarcomaRSNA Case Collection2021Esophageal Granular Cell Tumor RSNA Case Collection2022Gastric LeiomyomaRSNA Case Collection2021 Vol. 266, No. 3 Metrics Altmetric Score PDF download

IDH1-Associated Primary Glioblastoma in Young Adults Displays Differential Patterns of Tumour and Vascular Morphology

Glioblastoma is a highly aggressive tumour with marked heterogeneity at the morphological level in both the tumour cells and the associated highly prominent vasculature. As we begin to develop an increased biological insight into the underlying processes driving the disease, fewer attempts have thus far been made to understand these phenotypic differences. We sought to address this by carefully assessing the morphological characteristics of both the tumour cells and the associated vasculature, relating these observations to the IDH1/MGMT status, with a particular focus on the early onset population of young adults who develop primary glioblastoma. 276 primary glioblastoma specimens were classified into their predominant cell morphological type (fibrillary, gemistocytic, giant cell, small cell, oligodendroglial, sarcomatous), and assessed for specific tumour (cellularity, necrosis, palisades) and vascular features (glomeruloid structures, arcades, pericyte proliferation). IDH1 positive glioblastomas were associated with a younger age at diagnosis, better clinical outcome, prominent oligodendroglial and small cell tumour cell morphology, pallisading necrosis and glomeruloid vascular proliferation in the absence of arcade-like structures. These features widen the phenotype of IDH1 mutation-positive primary glioblastoma in young adults and provide correlative evidence for a functional role of mutant IDH1 in the differential nature of neo-angiogenesis in different subtypes of glioblastoma.

Defining Good Candidates for Extraperitoneal Cystectomy: Results From Random Peritoneum Biopsies of 136 Cases

To define who are good candidates for extraperitoneal cystectomy. Between April 2009 and April 2012, 136 consecutive patients (median age 63.8 years, range 35-87 years) scheduled for transperitoneal radical cystectomy were included in this study. After the bladder was removed, the peritoneum covering the bladder was detached. Any suspicious macroscopic abnormalities on the peritoneum were sampled and examined. A 6-8 point random biopsy of the peritoneum was performed for patients without gross macroscopic abnormality. The study group consisted of 41 patients with pT1, 48 patients with pT2, 34 patients with pT3, and13 patients with pT4. The transitional cell carcinoma (TCC) group consisted of 123 of 136patients (90.4%) and nonurothelial histologies of 13 of 136 patients (9.6%). In general, 8 of 136 patients (5.9%) and 14 of 816 biopsies (1.7%) were confirmed positive for peritoneum biopsies. Among them, 0 of 89 patients with pT1/2, 5 of 34 patients with pT3 (14.7%), and 3 of 13 patients with pT4 (23.1%) had positive biopsies (P<.001). In addition, 5 of 123 patients (4.9%) with TCC, 1 of 7 patients (14.3%) with adenocarcinoma, 1 of 2 patients (50%) with sarcomatoid carcinoma, and 1 of 2 patients (50%) with small cell tumors had positive peritoneum biopsies (P=.006). Among patients with positive lymph nodes, 5 of 34 patients (14.7%) had positive biopsies, compared with 3 of 102 patients (2.9%) in the lymph node-negative group (P=.012). We found that tumor stage and lymph node status are independent predictors of peritoneal involvement. Extraperitoneal cystectomy should be performed with great caution, only indicated for those patients who have a high likelihood of stage pT1 and pT2. However, patients with cT2-4, positive lymph nodes, or nonurothelial histologies should not have the peritoneum covering the bladder preserved.

31. EWSR1 FISH – an assessment of complex signal patterns

<h3>Background</h3> EWSR1 FISH is an extremely useful diagnostic tool in the identification of EWSR1 rearrangements that are involved in a broad variety of mesenchymal tumours such as Ewing sarcoma, desmoplastic small round cell tumour and clear cell sarcoma, among others. We have observed a number of lesions (EWSR1 related tumours and others) which displayed ‘non-classical' EWSR1 FISH signal patterns, which present a technical and diagnostic challenge. <h3>Aims</h3> To describe atypical patterns of the EWSR1 FISH break-apart probe in tumours. <h3>Methods</h3> EWSR1 FISH was performed using Vysis EWSR1 Break Apart FISH Probe Kit (Abbott Molecular) in a series of 4 cases. <h3>Results and conclusions</h3> We observed an unusual clavicular lesion in a 15-year-old boy favoured to represent a chondromyxoid fibroma with some atypical histological features displaying gain of the 5' EWSR1 locus in addition to loss of the 3' EWSR1 locus. A Ewing sarcoma showed the opposite pattern with loss of the 5' EWSR1 locus and gain of the 3' locus. A case of poorly differentiated breast carcinoma in a 22-year-old woman displayed gain of the 3' EWSR1 locus and a synovial sarcoma case (confirmed by FISH for SS18) also displayed loss of the 5' EWSR1 locus. In our experience poorly differentiated tumours may show atypical EWSR1 breakapart probe patterns. This collection of cases, potentially representing combinations of duplications, deletions, aneuploidy or pseudogene cross-reactivity, highlight the technical and diagnostic challenges of interpreting unusual EWSR1 rearrangements.

Adult Nephroblastoma with Predominant Epithelial Component: A Differential Diagnostic Candidate of Papillary Renal Cell Carcinoma and Metanephric Adenoma—Report of Three Cases

Although nephroblastoma is the commonest renal tumor of childhood, it is rare in adults. In cases of predominantly epithelial type occurring in adulthood, it might be difficult to distinguish it from papillary renal cell carcinoma and metanephric adenoma. Here, we report three cases of adult epithelial nephroblastoma in 24-, 76-, and 21-year-old females. Histologically, the tumors were composed of papillotubular architectures of small and uniform tumor cells with high nucleocytoplasmic ratio without blastemal element. Immunohistochemically, the tumor cells were positive for WT-1 and CD57 but negative for AMACR, which was helpful to exclude the possibility of papillary renal cell carcinoma. Metanephric adenoma is a benign tumor, which can be distinguished by the observation of the cellular atypism and growth pattern. However, nephroblastoma with predominant epithelial element mimics the malignant counterpart of metanephric adenoma, that is, “metanephric adenocarcinoma.”

Ovarian small cell carcinoma of hypercalcemic type – evidence of germline origin and smarca4 gene inactivation. a pilot study

Ovarian tumors from two patients, compatible by histological and immunohistochemical criteria with small cell carcinoma of hypercalcemic type (SCCHT) (WT1+, EMA dispersed+, synaptophysin+ or dispersed+), were extensively sampled in order to find clues to their histogenesis. Subsequently, small foci of immature teratoma were found in both of them (in 1/122 and in 3/80 tumor sections). In one case, microfoci of yolk sac tumor were also present within the teratoma area as well as in the background of the small cell tumor population - in the primary tumor and in omental metastasis. We found a resemblance of the microscopic patterns of SCCHT and atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, and this prompted us to evaluate INI-1 and SMARCA4 immunohistochemical expression, because their alternative loss is regarded as a molecular hallmark of AT/RT. INI-1 expression was retained, while that of SMARCA4 was lost. We therefore analyzed tumor DNA by PCR amplification and sequencing for mutations in the SMARCA4 gene (NG_011556.1), which were identified in both tumors (c.2184_2206del; nonsense c.3277C>T - both in one tumor; nonsense c.3760G>T in another tumor). These data suggest that SCCHT is most likely an embryonal tumor originating from immature teratoma and related to malignant rhabdoid tumor. Further analyses are necessary to determine whether the tumors diagnosed as SCCHT constitute a homogeneous group or represent more than one entity.

Nemeth-Kellner Lymphoma Is a Valid Experimental Model in Testing Chemical Agents for Anti-Lymphoproliferative Activity*

Scheme of detection and investigation of antitumor activity of chemical substances by use of experimental murine Nemeth-Kellner lymphoma (NK/Ly) are described. It includes monitoring of growth of NK/Ly ascites by everyday weighting of animals in course of intraperitoneal application of tested substance in 24 or 48 hours after inoculation of 107 tumor cells. The inhibitory effect became distinct on the 6th-8th day of experiment, and 3 types of response were observed: 1) complete suppression of ascites development, corresponding to high antitumor activity of tested substance; 2) partial suppression of ascites growth (weak antitumor activity); 3) insignificant effect on ascites growth (lack of activity, at least towards hematoblastoses). As compared with leukemia L1210 or P388 lymphoma NK/Ly provides more distinct daily increment of body weight due to tumor growth. Clinical pattern of tumor development was supported by cytomorphological investigations of tumor cells which included: 1) cells count in ascites; 2) measuring cell dimensions and ratio of enlarged cells in a population (diameter over 17 μm in case of NK/Ly); 3) quantitative evaluation of tumor cells damage by smears count after staining with azure-eosin, bromophenol blue and hematoxylin. In case of complete suppression of ascites growth the cytological investigation was conducted by delayed application of tested agent to animals with the developed ascites. After treatment with vinblastine or doxorubicin NK/Ly cells represent a convenient object for fractionation of cell population, as demonstrated by separation of giant and small tumor cell subpopulations.

Perineural Involvement in Benign Mixed Tumor

Perineural invasion is a diagnostic clue of malignancy and may be indicative of a poor prognosis. Perineural involvement of a benign tumor is diagnostically confusing, however, and should not be considered a malignant feature. We report a case of benign mixed tumor of the salivary gland with two foci of perineural involvement. A 31-year-old man complained of a right parotid mass which had been present for three months. He had no relevant medical history. On physical examination, there was a movable, round mass that was not accompanied by tenderness or redness. Computed tomography revealed an ovoid mass in the deep lobe of the right parotid gland with strong, early, heterogeneous enhancement. There was no evidence of tumor invasion into the surrounding tissue. Right parotidectomy was carried out; the specimen was a well-demarcated, firm, ovoid mass (2.5×2.0×1.5 cm). Grossly, the mass was grayish-tan and solid, with multifocal hemorrhages. Microscopic findings were those of a typical benign mixed tumor of the salivary gland, consisting of mixed epithelial and myoepithelial cells with chondromyxoid stroma. No lymphovascular invasion was identified. Interestingly, two foci of small tumor cell nests were present around and within nerve twigs, which were located in the subcapsular space and the fibrous tumor capsule (Fig. 1). Five months after the operation, neither recurrence nor metastasis was evident on follow-up examination. Perineural invasion is an important pathologic feature of malignancy and is related to poor outcome. However, certain benign neoplasms and reactive conditions can reveal perineural involvement. Mixed tumor is the most common type of salivary gland tumors and, in most patients, is benign, except for rare secondary malignant transformation. Typical features of malignancy are infiltrative growth, nuclear pleomorphism, atypical mitosis, necrosis, and lymphovascular or perineural invasion. The presented case had perineural involvement of benign tumor cells; otherwise it exhibited characteristics of a benign mixed tumor. The important thing to consider here is the significance of perineural involvement in the biologic behavior of the tumor. Perineural involvement of benign lesions has been documented not only in the head and neck, but also in other sites. Benign mammary glandular deposits in nerves were first described by Ali and Epstein1 and other cases of benign tumor deposits of the breast, prostate, pancreas, gallbladder, endometrium, and skin have been reported in the literature. There have been no reported cases of benign mixed tumor of salivary gland with perineural involvement in Korea. Although the cause and mechanism of perineural involvement cannot be clearly defined, Skidmore et al.2 suggested a mechanical stress origin for perineural involvement of benign tumors, but theories regarding the mechanism of its development have yet to be proven. In the present case, fine needle aspiration was performed on the tumor a month prior to the operation, which may be a potential cause of mechanical stress. In conclusion, a histologically-benign mixed tumor of the salivary gland with perineural involvement should not be diagnosed as a malignant tumor without other evidence of malignancy.