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Item Characteristics of testicular tumors in prepubertal children (age 5–12 years)(Elsevier, 2018) Karmazyn, Boaz; Weatherly, David L.; Lehnert, Stephen J.; Cain, Mark; Fan, Rong; Jennings, S. Gregory; Ouyang, Fangqian; Kaefer, Martin; Radiology and Imaging Sciences, School of MedicineIntroduction Testicular tumors in children have two peaks with different types of tumors; in the first 4 years of life a third to half are benign with increased risk of malignancy during puberty. The pathology of testicular tumors between these peaks, at the age of 5–12 years, is not known. We hypothesized that because of the low level of testosterone at this time, the incidence of malignant tumors is very low. Objective To compare malignancy risk of primary testicular tumors in children in the prepubertal period (5–12 years) compared with younger (0–4 years) and pubertal (13–18 years) children. Study design We retrospectively (2002–2016) identified patients <18 years with surgery for primary testicular tumor. Patients with testicular tumor risk were excluded. Ultrasound studies were reviewed for contralateral testis volume, tumor morphology, and tumor maximal diameter, for three age groups: 0–4, 5–12, and 13–18 years. The Freeman-Halton extension of the Fisher exact probability test was adopted for categorical outcomes, and one-way ANOVA for continuous outcomes. Results Fifty-two patients (mean age 11.0 years, range 6 days–18 years) were identified. Malignant tumor prevalence significantly differed ( p < 0.01) among age groups ( Fig ).: 0–4 (72.7%, 8/11), 5–12 (0%, 0/16), and 13–18 years (44.0%, 11/25). The most common tumor types in 5–12 years were epidermoid cyst (31.3%, 5/16) and tumor mimics (37.5%, 6/16). Prevalence of cystic tumors in 5–12 year olds was not significantly different compared with other age groups. Contralateral testicular volume >4 mL (pubertal surge) significantly ( p < 0.01) differed among groups: 0–4 years (0/11), 5–12 years (3/16), and 13–18 years (19/20). In children aged 13–18 years the mean tumor maximal diameter (29.8 ± 4.4 mm) was significantly larger (p < 0.01) compared with children 5–12 years (9.3 ± 5.5 mm) and all malignant tumors had contralateral testicular volume >4 mL. Discussion We found that preadolescent children between the ages of 5 and 12 years have distinctive characteristics compared with the other age groups. Most importantly, no malignant testicular tumors were found in this age group. About a third of the children presented with an incidental testicular mass. The testicular tumors were significantly smaller (9.3 ± 6.7 mm) compared with those in children aged 13–18 years (29.8 ± 4.4 mm). There were limitations because of the retrospective nature of the study. Conclusion We found no malignant testicular tumors in children aged 5–12 years with no risk factors and prior to pubertal surge. Our study suggests use of more conservative treatment in this group of patients.Item Evidence of a dual histogenetic pathway of sacrococcygeal teratomas(Wiley, 2017-01) Emerson, Robert E.; Kao, Chia-Sui; Eble, John N.; Grignon, David J.; Wang, Mingsheng; Zhang, Shaobo; Wang, Xiaoyan; Fan, Rong; Masterson, Timothy A.; Roth, Lawrence M.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of MedicineAims Sacrococcygeal teratomas are rare tumours that occur most frequently in neonates, although adult cases also occur. The molecular pathogenesis of these tumours and their long-term prognosis is uncertain. We investigated the i(12p) status of a large number of primary sacrococcygeal teratomas in both children and adults, including cases with malignant germ cell tumour elements. Methods and results Fifty-four sacrococcygeal teratoma specimens from 52 patients were identified, and available follow-up information was obtained. Fluorescence in-situ hybridization analysis was performed to identify isochromosome 12p [i(12p)] abnormalities on paraffin blocks of the tumours. Among the 48 paediatric patients, there were 44 teratomas and four tumours with combined teratoma and yolk sac tumour (one of whom also had primitive neuroectodermal tumour). The teratomas included 37 mature teratomas and 11 immature teratomas (four grade 1, two grade 2, and five grade 3). The 44 teratomas lacking a yolk sac tumour component were all negative for i(12p). The four tumours with a yolk sac tumour component were all positive for i(12p). The four adult cases all lacked non-teratomatous germ cell tumour components, immature elements, and i(12p). Follow-up information was available for 32 patients. Two patients with teratoma had recurrence, but were alive with no evidence of disease after long-term follow-up. One patient with combined teratoma and yolk sac tumour had recurrence 7 months after resection. The other patients were alive with no evidence of disease at last follow-up. Conclusions Our data suggest that paediatric sacrococcygeal teratomas should be considered as two distinct groups with divergent histogenetic pathways. The prognosis of these tumours is excellent, despite rare recurrence.Item Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes(Wiley, 2019-02-10) Xiao, Yang; Kim, Dongjoo; Dura, Burak; Zhang, Kerou; Yan, Runchen; Li, Huamin; Han, Edward; Ip, Joshua; Zou, Pan; Liu, Jun; Chen, Ann Tai; Vortmeyer, Alexander O.; Zhou, Jiangbing; Fan, Rong; Pathology and Laboratory Medicine, School of MedicineThe perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature-on-a-chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single-cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions.Item Pediatric intraosseous cranial myxoma: A case report and review of literature(Wiley, 2021-10-15) Howser, Lauren A.; Ye, Michael J.; Boham, Sampson; Fan, Rong; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineWhile intraosseous cranial myxoma is a rare pathology, it is important for providers to be aware of it, as early diagnosis and treatment is imperative for prognosis. Long‐term follow‐up is needed as high rates of recurrence have been documented.Item qPCR is a sensitive and rapid method for detection of cytomegaloviral DNA in formalin-fixed, paraffin-embedded biopsy tissue(MyJoVE Corporation, 2014-07-09) McCoy, Morgan H.; Post, Kristin; Sen, Joyashree D.; Chang, Hsim Y.; Zhao, Zijin; Fan, Rong; Chen, Shaoxiong; Leland, Diane; Cheng, Liang; Lin, Jingmei; Department of Pathology and Laboratory Medicine, IU School of MedicineIt is crucial to identify cytomegalovirus (CMV) infection in the gastrointestinal (GI) tract of immunosuppressed patients, given their greater risk for developing severe infection. Many laboratory methods for the detection of CMV infection have been developed, including serology, viral culture, and molecular methods. Often, these methods reflect systemic involvement with CMV and do not specifically identify local tissue involvement. Therefore, detection of CMV infection in the GI tract is frequently done by traditional histology of biopsy tissue. Hematoxylin and eosin (H&E) staining in conjunction with immunohistochemistry (IHC) have remained the mainstays of examining these biopsies. H&E and IHC sometimes result in atypical (equivocal) staining patterns, making interpretation difficult. It was shown that quantitative polymerase chain reaction (qPCR) for CMV can successfully be performed on formalin-fixed, paraffin-embedded (FFPE) biopsy tissue for very high sensitivity and specificity. The goal of this protocol is to demonstrate how to perform qPCR testing for the detection of CMV in FFPE biopsy tissue in a clinical laboratory setting. This method is likely to be of great benefit for patients in cases of equivocal staining for CMV in GI biopsies.Item Williams Syndrome With Rare Ureteric Abnormality(Cureus, 2021-08-16) Khan, Jaffar; Al-Obaidy, Khaleel I.; Fan, Rong; Pathology and Laboratory Medicine, School of MedicineWilliams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by infantile hypercalcemia, short stature, a varying degree of mental retardation, elfin-like facial features, and cardiovascular abnormalities, including systemic hypertension, aortic hypoplasia, coarctation of the aorta, and valvular heart disease (aortic and pulmonic stenosis, mitral valve prolapsed or bicuspid aortic valve). It is also characterized by friendly and outgoing personality. The majority of WS cases are sporadic, while few are familial. Both sporadic and familial cases are due to deletion of chromosome 7 (7q11.23). Herein, we present an autopsy case of a 16-day-old male infant born to a 25-year-old mother with a history of William syndrome. Prenatal echocardiogram showed supravalvular aortic stenosis and pulmonary stenosis. The postnatal course was complicated by feeding difficulties and desaturation. Gross autopsy findings included generalized edema, macrocephaly with short neck, and multiple facial anomalies (mandibular hypoplasia, depressed nasal bridge, long philtrum, ear malformation, and wide mouth). The heart was hypertrophied with obstructed ventricles and rudimentary, hypoplastic aortic root. An enlarged, dilated, and tortuous left ureter was a unique finding to this case, in addition to variation in the renal arteries' size and an small bowel outpouching located 33 cm from the ileocecal valve. Cytogenetic analysis revealed deletion of chromosome 7 (7q11.23). In conclusion, majority of WS cases are sporadic, and few are familial and are inherited as autosomal dominant.