Bio

Clinical Focus


  • Anatomic and Clinical Pathology

Academic Appointments


Professional Education


  • Board Certification, Pediatric Pathology, American Board of Pathology (2019)
  • Board Certification: American Board of Pathology, Anatomic and Clinical Pathology (2017)
  • Fellowship: Ann and Robert H Lurie Children's Hospital Pediatric Pathology Fellowship (2019) IL
  • Fellowship: Stanford University Surgical Pathology Fellowship (2018) CA
  • Residency: Stanford University Pathology Residency (2017) CA
  • Medical Education: Duke University School of Medicine (2008) NC

Publications

All Publications


  • Capillary cell-type specialization in the alveolus. Nature Gillich, A., Zhang, F., Farmer, C. G., Travaglini, K. J., Tan, S. Y., Gu, M., Zhou, B., Feinstein, J. A., Krasnow, M. A., Metzger, R. J. 2020

    Abstract

    In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood1. Here we use single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries are mosaics; similar to the epithelium that lines the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex 'Swiss-cheese'-like morphologies and distinct functions. The first cell type, which we term the 'aerocyte', is specialized for gas exchange and the trafficking of leukocytes, and is unique to the lung. The other cell type, termed gCap ('general' capillary), is specialized to regulate vasomotor tone, and functions as a stem/progenitor cell in capillary homeostasis and repair. The two cell types develop from bipotent progenitors, mature gradually and are affected differently in disease and during ageing. This cell-type specialization is conserved between mouse and human lungs but is not found in alligator or turtle lungs, suggesting it arose during the evolution of the mammalian lung. The discovery of cell type specialization in alveolar capillaries transforms our understanding of the structure, function, regulation and maintenance of the air-blood barrier and gas exchange in health, disease and evolution.

    View details for DOI 10.1038/s41586-020-2822-7

    View details for PubMedID 33057196

  • Barrett Esophagus and Intestinal Metaplasia of the Gastroesophageal Junction in Children: A Clinicopathologic Study. Journal of pediatric gastroenterology and nutrition Putra, J., Arva, N. C., Tan, S. Y., Melin-Aldana, H., Bass, L. M., Mitchell, P. D., Fox, V. L., Goldsmith, J. D. 2020; 70 (5): 562?67

    Abstract

    Barrett esophagus (BE) and intestinal metaplasia of gastroesophageal junction (IMGEJ) are rare in the pediatric population. This multi-institutional retrospective study evaluated the clinicopathologic characteristics and natural history of BE and IMGEJ in children.Data from 20 BE patients (70% boys, mean age: 14.9 years) and 17 IMGEJ patients (71% boys, mean age: 14 years) were retrospectively obtained from chart review. Endoscopic and pathologic findings from index and follow-up endoscopies were analyzed.Most patients (70% BE and 59% IMGEJ) had underlying conditions which put them at risk for gastroesophageal reflux disease. Increased body mass index (BMI) was observed in patients without underlying conditions (BE: 30.1?±?9.8; IMGEJ: 23.9?±?6.3) compared with those with underlying conditions (BE: 19.6?±?7.8; IMGEJ: 16.4?±?2.1) (BE, P?=?0.02; IMGEJ, P?=?0.01). Incomplete intestinal metaplasia (IM) was the predominant histology seen in BE (80%) and IMGEJ patients (75%). Dysplasia and malignancy were not identified in the initial and follow-up biopsies. Concurrent gastric biopsies showed various findings (79% BE and 40% IMGEJ were normal), with 1 IMGEJ patient showing coexisting gastric IM (7%). Follow-up in 12 BE patients (mean follow-up time 51.6 months) showed 100% persistent endoscopic disease and 58% persistent IM histologically. Three of 6 IMGEJ patients (mean follow-up time 24 months) demonstrated endoscopic and histologic features consistent with BE on subsequent procedures. Moreover, a subset of BE (57%) and IMGEJ patients (67%) who underwent endoscopy before initial diagnosis showed nongoblet columnar mucosa above the anatomic gastroesophageal junction.Increased BMI may be a risk factor for BE and IMGEJ in pediatric patients without underlying conditions. Nongoblet columnar metaplasia and IMGEJ might represent incomplete forms of BE. Our data suggest that these patients should be closely monitored.

    View details for DOI 10.1097/MPG.0000000000002640

    View details for PubMedID 31977949

  • Gonadal Tissue Cryopreservation for Children with Differences of Sex Development HORMONE RESEARCH IN PAEDIATRICS Johnson, E. K., Finlayson, C., Finney, E. L., Harris, C. J., Tan, S. Y., Laronda, M. M., Lockart, B. A., Chen, D., Rowell, E. E., Cheng, E. Y., Yerkes, E. B. 2020; 92 (2): 84?91

    Abstract

    Infertility is common for individuals with differences of sex development (DSD) and is a significant concern to these individuals. Fertility potential in many DSD conditions is poorly understood. Gonadal tissue cryopreservation (GTC) for fertility preservation (FP) is offered to children with cancer undergoing gonadotoxic therapy. Our team sought to expand the field of FP by offering and evaluating the success of GTC for individuals with DSD.GTC was offered to patients with DSD undergoing prophylactic gonadectomy, after extensive multidisciplinary counseling. For those who elected to attempt GTC, data were retrospectively abstracted, including: DSD diagnosis, age at gonadectomy, indication for gonadectomy, pathology results, and final decision about long-term gonadal tissue storage.Ten patients were enrolled to attempt GTC, with a mean age of 11.5 years (range 1-18). Five of the 10 patients had germ cells (GCs) present. Diagnoses (age at gonadectomy) for patients with GCs included ovotesticular DSD (13 months), mixed gonadal dysgenesis (17 months), partial gonadal dysgenesis (3 years), partial androgen insensitivity syndrome (11 years), and mixed gonadal dysgenesis (12 years). Four of the 5 subjects with GCs elected for GTC. One opted against GTC, citing immature gametes that did not match gender identity.GTC at the time of gonadectomy for patients with DSD is feasible. In many patients, GCs are present. While questions remain about the timing of gonadectomy, quality of GCs, and future success for use of the tissue based on technological advancement, GTC represents a novel approach to experimental FP for individuals with DSD.

    View details for DOI 10.1159/000502644

    View details for Web of Science ID 000507907900002

    View details for PubMedID 31509845

  • Dissecting the Cardiac Conduction System: Is It Worthwhile? Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society Tan, S. Y., Fritsch, M. K., White, S., Arva, N. C. 2020: 1093526620944756

    Abstract

    Pathologic examination of conduction system (CS) is not routinely performed, and histologic changes are mostly reported in forensic practice.We studied the value of dissecting the CS in a cohort of pediatric patients with unexplained sudden death or severe, inexplicable arrhythmias. Histopathologic changes present in CS components were recorded and correlated with findings noted in other cardiac structures.Twenty-one subjects (11 unexplained sudden deaths and 10 life-threatening arrhythmias) were identified; 18 (86%) had CS pathologic abnormalities. In 13 patients (62%), the CS findings mirrored those found in other cardiac sections (inflammation, allograft vasculopathy, vascular fibromuscular dysplasia, cardiomyopathy-related changes, and tumor/tumor-like conditions). Five cases (24%) had abnormalities restricted to CS (bundle of His [BH] with fibrotic scar and patch material following ventricular septal defect repair, inflammation, BH with fibrosis and calcifications, and intimal fibroplasia of sinoatrial node artery).Pathologic changes within the CS are present in a high number of pediatric patients presenting with unexplained sudden death or life-threatening arrhythmias. Frequently, the findings mirror those observed in other cardiac structures. However, in a significant number of cases (24%), the changes are restricted to CS and likely explain the patients' symptoms or cause of death, suggesting that systematic dissection of CS unveils valuable information.

    View details for DOI 10.1177/1093526620944756

    View details for PubMedID 32755444

  • Solitary Fibrous Tumors in Pediatric Patients: A Rare and Potentially Overdiagnosed Neoplasm, Confirmed by STAT6 Immunohistochemistry PEDIATRIC AND DEVELOPMENTAL PATHOLOGY Tan, S. Y., Szymanski, L. J., Galliani, C., Parham, D., Zambrano, E. 2018; 21 (4): 389?400
  • Thrombotic Microangiopathy with Intraglomerular Monoclonal IgM Pseudothrombi Tan, S., Sibley, R., Higgins, J., Kambham, N., Troxell, M. NATURE PUBLISHING GROUP. 2018: 618
  • Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 2018; 562 (7727): 367?72

    Abstract

    Here we present a compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. The cumulative data provide the foundation for an atlas of transcriptomic cell biology.

    View details for DOI 10.1038/s41586-018-0590-4

    View details for PubMedID 30283141

  • Pleomorphic myxoid liposarcoma in an adolescent with Li-Fraumeni syndrome. Pediatric surgery international Sinclair, T. J., Thorson, C. M., Alvarez, E., Tan, S., Spunt, S. L., Chao, S. D. 2017

    Abstract

    We present the case of a 15-year-old female with a right perineal mass that was found to be pleomorphic myxoid liposarcoma, a recently recognized, rare subtype of liposarcoma. The patient had a strong family history of malignancy and genetic screening revealed a pathogenic TP53 mutation consistent with Li-Fraumeni syndrome.

    View details for DOI 10.1007/s00383-017-4063-x

    View details for PubMedID 28160093

  • BRAF inhibitor treatment of primary BRAF-mutant ameloblastoma with pathologic assessment of response ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY Tan, S., Pollack, J. R., Kaplan, M. J., Colevas, A. D., West, R. B. 2016; 122 (1): E5-E7

    Abstract

    Molecular characterization of ameloblastoma has indicated a high frequency of driver mutations in BRAF and SMO. Preclinical data suggest that Food and Drug Administration-approved BRAF-targeted therapies may be immediately relevant for patients with ameloblastoma positive for the BRAF V600E mutation.A neoadjuvant treatment regime of dabrafenib was given to a patient with recurrent BRAF-mutant mandibular ameloblastoma. The patient subsequently underwent left mandible composite resection of the tumor and pathologic evaluation of treatment response.The ameloblastoma had a slow but dramatic response with >90% tumor volume reduction. The inner areas of the tumor underwent degeneration and squamous differentiation, and intact ameloblastoma was present in the outer areas associated with bone.Targeted neoadjuvant therapy for ameloblastoma may be useful in certain clinical settings of primary ameloblastoma. These might include tumors of advanced local stage when a neoadjuvant reduction could alter the extent of surgery and instances of local recurrence when surgical options are limited.

    View details for DOI 10.1016/j.oooo.2015.12.016

    View details for Web of Science ID 000377426600002

    View details for PubMedID 27209484

  • Developmental origin of lung macrophage diversity DEVELOPMENT Tan, S. Y., Krasnow, M. A. 2016; 143 (8): 1318-1327

    Abstract

    Macrophages are specialized phagocytic cells, present in all tissues, which engulf and digest pathogens, infected and dying cells, and debris, and can recruit and regulate other immune cells and the inflammatory response and aid in tissue repair. Macrophage subpopulations play distinct roles in these processes and in disease, and are typically recognized by differences in marker expression, immune function, or tissue of residency. Although macrophage subpopulations in the brain have been found to have distinct developmental origins, the extent to which development contributes to macrophage diversity between tissues and within tissues is not well understood. Here, we investigate the development and maintenance of mouse lung macrophages by marker expression patterns, genetic lineage tracing and parabiosis. We show that macrophages populate the lung in three developmental waves, each giving rise to a distinct lineage. These lineages express different markers, reside in different locations, renew in different ways, and show little or no interconversion. Thus, development contributes significantly to lung macrophage diversity and targets each lineage to a different anatomical domain.

    View details for DOI 10.1242/dev.129122

    View details for Web of Science ID 000385261300010

    View details for PubMedID 26952982

    View details for PubMedCentralID PMC4852511

  • A novel laparoscopic-assisted approach to the repair of pediatric femoral hernias. Journal of laparoendoscopic & advanced surgical techniques. Part A Tan, S. Y., Stevens, M. J., Mueller, C. M. 2013; 23 (11): 946-948

    Abstract

    Abstract Background: Femoral hernias in young children are relatively rare and can be difficult to diagnose as they are often mistaken for inguinal hernias. Although a few reports have described laparoscopic techniques, most traditional repair methods still focus on an open approach using either an inguinal or crural incision. Here we describe a laparoscopic-assisted technique that is buttressed by a cigarette of mesh for the repair of this uncommon pediatric entity. Subjects and Methods: We report three consecutive cases of children with femoral hernias repaired with only two small incisions: a 5-mm umbilical incision for a 30° camera and a 1-cm groin incision for dissection and ligation of the hernia sac. After sac ligation, the repair was buttressed with a small mesh cigarette. Results: Using this approach, right femoral hernias were repaired without complication in three children, between 8 and 9 years of age. Two patients had ipsilateral indirect inguinal hernias. No contralateral groin hernias were identified in any of the patients. Operative time averaged 40 minutes, recovery time was quick, and follow-up at 6 months revealed good cosmesis. Conclusions: This laparoscopic-assisted approach to pediatric femoral hernia repair with a small mesh plug is a safe, effective, and efficient technique. Because only two incisions are required, postoperative pain is minimal, and cosmesis is excellent. Nonetheless, more patients and longer follow-up will be required to accurately judge the long-term implications of this novel technique.

    View details for DOI 10.1089/lap.2013.0199

    View details for PubMedID 24015871

  • Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia JOURNAL OF CLINICAL INVESTIGATION Tan, S. Y., Rosenthal, J., Zhao, X., Francis, R. J., Chatterjee, B., Sabol, S. L., Linask, K. L., Bracero, L., Connelly, P. S., Daniels, M. P., Yu, Q., Omran, H., Leatherbury, L., Lo, C. W. 2007; 117 (12): 3742-3752

    Abstract

    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder associated with ciliary defects and situs inversus totalis, the complete mirror image reversal of internal organ situs (positioning). A variable incidence of heterotaxy, or irregular organ situs, also has been reported in PCD patients, but it is not known whether this is elicited by the PCD-causing genetic lesion. We studied a mouse model of PCD with a recessive mutation in Dnahc5, a dynein gene commonly mutated in PCD. Analysis of homozygous mutant embryos from 18 litters yielded 25% with normal organ situs, 35% with situs inversus totalis, and 40% with heterotaxy. Embryos with heterotaxy had complex structural heart defects that included discordant atrioventricular and ventricular outflow situs and atrial/pulmonary isomerisms. Variable combinations of a distinct set of cardiovascular anomalies were observed, including superior-inferior ventricles, great artery alignment defects, and interrupted inferior vena cava with azygos continuation. The surprisingly high incidence of heterotaxy led us to evaluate the diagnosis of PCD. PCD was confirmed by EM, which revealed missing outer dynein arms in the respiratory cilia. Ciliary dyskinesia was observed by videomicroscopy. These findings show that Dnahc5 is required for the specification of left-right asymmetry and suggest that the PCD-causing Dnahc5 mutation may also be associated with heterotaxy.

    View details for DOI 10.1172/JCI33284

    View details for Web of Science ID 000251396600023

    View details for PubMedID 18037990

    View details for PubMedCentralID PMC2082149

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